Pub Date : 2025-01-29DOI: 10.1016/j.biocel.2025.106741
Lei Zheng , Shuling Han , Olivia M Martinez , Sheri M Krams
Background and Aims
Liver ischemia-reperfusion injury (LIRI) profoundly affects liver function and survival largely through activation of the innate immune system. In this study we sought to elucidate the underlying mechanisms by which the innate immune system impacts liver function and survival in LIRI.
Approach and Results
RNA-seq analyses, from existing datasets of liver from mice with LIRI, was performed to identify differentially expressed genes (DEGs) associated with LIRI. Protein-protein interaction analysis revealed clusters involved in signaling pathways with a cluster anchored by Senp2, acting as a central modulator. Macrophages and monocytes were determined to be the source of Senp2 with monocyte-derived macrophages expressing the highest levels of Senp2. Experiments in a mouse model of LIRI further elucidated the expression, function, and mechanism of Senp2. Overexpression of Senp2 suppressed both the polarization of M1 macrophages and the production of inflammatory mediators. Further, Senp2-overexpressing macrophages significantly ameliorated LIRI.
Conclusions
Our study suggests that SENP2 plays an important role in regulating LIRI by influencing macrophage polarization through the Dvl2/GSK-3β/β-catenin axis. While further validation is needed, these findings indicate that targeting SENP2-mediated pathways could be a promising approach for mitigating LIRI and enhancing therapeutic strategies.
{"title":"SENP2 as a critical regulator in liver ischemia-reperfusion injury","authors":"Lei Zheng , Shuling Han , Olivia M Martinez , Sheri M Krams","doi":"10.1016/j.biocel.2025.106741","DOIUrl":"10.1016/j.biocel.2025.106741","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Liver ischemia-reperfusion injury (LIRI) profoundly affects liver function and survival largely through activation of the innate immune system. In this study we sought to elucidate the underlying mechanisms by which the innate immune system impacts liver function and survival in LIRI.</div></div><div><h3>Approach and Results</h3><div>RNA-seq analyses, from existing datasets of liver from mice with LIRI, was performed to identify differentially expressed genes (DEGs) associated with LIRI. Protein-protein interaction analysis revealed clusters involved in signaling pathways with a cluster anchored by Senp2, acting as a central modulator. Macrophages and monocytes were determined to be the source of Senp2 with monocyte-derived macrophages expressing the highest levels of Senp2. Experiments in a mouse model of LIRI further elucidated the expression, function, and mechanism of Senp2. Overexpression of Senp2 suppressed both the polarization of M1 macrophages and the production of inflammatory mediators. Further, Senp2-overexpressing macrophages significantly ameliorated LIRI.</div></div><div><h3>Conclusions</h3><div>Our study suggests that SENP2 plays an important role in regulating LIRI by influencing macrophage polarization through the Dvl2/GSK-3β/β-catenin axis. While further validation is needed, these findings indicate that targeting SENP2-mediated pathways could be a promising approach for mitigating LIRI and enhancing therapeutic strategies.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106741"},"PeriodicalIF":3.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-25DOI: 10.1016/j.biocel.2025.106738
Zihe Zheng , Wei Wang , Ming Huang , Bo Chen , Tao Wang , Zheng Xu , Xin Jiang , Xiaofu Dai
Background
Heart failure is linked to increased hospitalization and mortality. Mitochondrial permeability transition-driven necrosis is associated with cardiovascular diseases, but its role in heart failure is unclear. This study aimed to identify and validate genes related to mitochondrial permeability transition-driven necrosis in heart failure, potentially leading to new drug targets and signaling pathways.
Methods
We identified differentially expressed genes related to heart failure from the gene expression omnibus database and identified module genes related to mitochondrial permeability transition-driven necrosis from the gene set enrichment analysis database. Key genes were determined by intersecting these two gene groups using least absolute shrinkage and selection operator and support vector machine algorithms. Pathways, diagnostic efficacy, gene interactions, immune infiltration, and regulatory networks were analyzed. Small interfering RNAs were used for validation. Real-time-quantitative polymerase chain reaction, flow cytometry, and JC1 assays were performed in vitro.
Results
Forty-six differentially expressed genes, and 3439 module genes were identified. LYVE1, IL1RL1, and SERPINA3 were identified as significantly downregulated key genes, with IL1RL1 and SERPINA3 associated with heart failure risk. Benzo(a) pyrene, bisphenol A, estradiol, and particulate matter were found to simultaneously increase the expression of three key genes. In clinical samples, only LYVE1 and IL1RL1 were downregulated, as expected. Knockdown of these genes in cells led to increased necrosis and decreased mitochondrial membrane potential. Only estradiol reduced brain natriuretic peptide protein levels in hypertrophic cells.
Conclusions
LYVE1 and IL1RL1 were validated as key genes linked to mitochondrial permeability transition-driven necrosis in heart failure. Estradiol may have a therapeutic effect on heart failure.
{"title":"LYVE1 and IL1RL1 are mitochondrial permeability transition-driven necrosis-related genes in heart failure","authors":"Zihe Zheng , Wei Wang , Ming Huang , Bo Chen , Tao Wang , Zheng Xu , Xin Jiang , Xiaofu Dai","doi":"10.1016/j.biocel.2025.106738","DOIUrl":"10.1016/j.biocel.2025.106738","url":null,"abstract":"<div><h3>Background</h3><div>Heart failure is linked to increased hospitalization and mortality. Mitochondrial permeability transition-driven necrosis is associated with cardiovascular diseases, but its role in heart failure is unclear. This study aimed to identify and validate genes related to mitochondrial permeability transition-driven necrosis in heart failure, potentially leading to new drug targets and signaling pathways.</div></div><div><h3>Methods</h3><div>We identified differentially expressed genes related to heart failure from the gene expression omnibus database and identified module genes related to mitochondrial permeability transition-driven necrosis from the gene set enrichment analysis database. Key genes were determined by intersecting these two gene groups using least absolute shrinkage and selection operator and support vector machine algorithms. Pathways, diagnostic efficacy, gene interactions, immune infiltration, and regulatory networks were analyzed. Small interfering RNAs were used for validation. Real-time-quantitative polymerase chain reaction, flow cytometry, and JC<img>1 assays were performed <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Forty-six differentially expressed genes, and 3439 module genes were identified. <em>LYVE1</em>, <em>IL1RL1</em>, and <em>SERPINA3</em> were identified as significantly downregulated key genes, with <em>IL1RL1</em> and <em>SERPINA3</em> associated with heart failure risk. Benzo(a) pyrene, bisphenol A, estradiol, and particulate matter were found to simultaneously increase the expression of three key genes. In clinical samples, only <em>LYVE1</em> and <em>IL1RL1</em> were downregulated, as expected. Knockdown of these genes in cells led to increased necrosis and decreased mitochondrial membrane potential. Only estradiol reduced brain natriuretic peptide protein levels in hypertrophic cells.</div></div><div><h3>Conclusions</h3><div><em>LYVE1</em> and <em>IL1RL1</em> were validated as key genes linked to mitochondrial permeability transition-driven necrosis in heart failure. Estradiol may have a therapeutic effect on heart failure.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106738"},"PeriodicalIF":3.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.biocel.2025.106735
Dietrich E. Lorke , Murat Oz
Acetylcholinesterase inhibition, the principal mechanism of acute organophosphorus compound toxicity, cannot explain neuropsychiatric symptoms occurring after exposure to low organophosphate concentrations causing no cholinergic symptoms. Organophosphate-triggered oxidative stress has increasingly come into focus, occurring when the action of reactive oxygen species, generated from free radicals, is not compensated by antioxidant free radical scavengers. Being nucleophilic, organophosphates can easily accept an electron, thereby generating free radicals. Organophosphates inhibit the antioxidant paraoxonase, and reactive oxygen species are produced during organophosphate metabolism. Organophosphates disrupt the function of mitochondria, the principal source of free radicals. Organophosphates also induce neuroinflammation, which generates reactive oxygen species, and reactive oxygen species in turn stimulate neuroinflammation. Markers of reactive oxygen species are elevated in vitro and in vivo after exposure to organophosphates and in individuals professionally exposed to organophosphates. This most probably contributes to the pathogenesis of the intermediate syndrome, chronic organophosphate-induced neuropsychiatric disorders and neurodegeneration occurring in patients after organophosphate exposure. Evidence for beneficial effects of antioxidants in organophosphate poisoning is discussed.
{"title":"A review on oxidative stress in organophosphate-induced neurotoxicity","authors":"Dietrich E. Lorke , Murat Oz","doi":"10.1016/j.biocel.2025.106735","DOIUrl":"10.1016/j.biocel.2025.106735","url":null,"abstract":"<div><div>Acetylcholinesterase inhibition, the principal mechanism of acute organophosphorus compound toxicity, cannot explain neuropsychiatric symptoms occurring after exposure to low organophosphate concentrations causing no cholinergic symptoms. Organophosphate-triggered oxidative stress has increasingly come into focus, occurring when the action of reactive oxygen species, generated from free radicals, is not compensated by antioxidant free radical scavengers. Being nucleophilic, organophosphates can easily accept an electron, thereby generating free radicals. Organophosphates inhibit the antioxidant paraoxonase, and reactive oxygen species are produced during organophosphate metabolism. Organophosphates disrupt the function of mitochondria, the principal source of free radicals. Organophosphates also induce neuroinflammation, which generates reactive oxygen species, and reactive oxygen species in turn stimulate neuroinflammation. Markers of reactive oxygen species are elevated <em>in vitro</em> and <em>in vivo</em> after exposure to organophosphates and in individuals professionally exposed to organophosphates. This most probably contributes to the pathogenesis of the intermediate syndrome, chronic organophosphate-induced neuropsychiatric disorders and neurodegeneration occurring in patients after organophosphate exposure. Evidence for beneficial effects of antioxidants in organophosphate poisoning is discussed.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106735"},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-21DOI: 10.1016/j.biocel.2025.106739
Anita Valand , Poojitha Rajasekar , Louise V. Wain , Rachel L. Clifford
Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms. This review provides an overview of the current understanding of the interplay between genetics and epigenetics in lung fibrosis. We discuss the genetic variants associated with susceptibility to lung fibrosis and explore how epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNA expression contribute to disease. Insights from genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) are integrated to explore the molecular mechanisms underlying lung fibrosis pathogenesis. We also discuss the potential clinical implications of genetics and epigenetics in lung fibrosis, including the development of novel therapeutic targets. Overall, this review highlights the importance of considering both genetic and epigenetic factors in the understanding and management of lung fibrosis.
{"title":"Interplay between genetics and epigenetics in lung fibrosis","authors":"Anita Valand , Poojitha Rajasekar , Louise V. Wain , Rachel L. Clifford","doi":"10.1016/j.biocel.2025.106739","DOIUrl":"10.1016/j.biocel.2025.106739","url":null,"abstract":"<div><div>Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms. This review provides an overview of the current understanding of the interplay between genetics and epigenetics in lung fibrosis. We discuss the genetic variants associated with susceptibility to lung fibrosis and explore how epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNA expression contribute to disease. Insights from genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) are integrated to explore the molecular mechanisms underlying lung fibrosis pathogenesis. We also discuss the potential clinical implications of genetics and epigenetics in lung fibrosis, including the development of novel therapeutic targets. Overall, this review highlights the importance of considering both genetic and epigenetic factors in the understanding and management of lung fibrosis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106739"},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20DOI: 10.1016/j.biocel.2025.106736
Ehsan Ahmadpour , Kimia Moradi , Reyhaneh Moghaddami , Rafieh Bagherifar , Arshad Ghaffari-Nasab , Mahdi Mahdipour , Azadeh Mizani , Mahdi Ahmadi , Monir Khordadmehr , Mohammad Hasan Kohansal
Cystic echinococcosis, caused by Echinococcus granulosus, is a zoonotic disease with immunomodulatory properties attributed to hydatid cyst fluid (HCF). Given the immune-modulating and anti-inflammatory properties of HCF observed in other contexts, its potential therapeutic effects in diabetes remain unexplored. This study aimed to investigate the potential therapeutic effects of HCF on glycemic control, inflammatory cytokines, and tissue histopathology in a streptozotocin (STZ)-induced model of type 1 diabetes. Twenty male rats were randomly divided into four groups (n = 5): a healthy control group, a hydatid cyst group that received three intraperitoneal injections of HCF at two-week intervals, a diabetic group that received a single intraperitoneal dose of STZ to induce diabetes, and a hydatid cyst + diabetic group (HCF + STZ) that received both HCF treatment and STZ administration. Serum glucose levels, inflammatory cytokines (TNF-α, IL-1β, and IL-10), and histopathological changes in pancreatic and renal tissues were analyzed. The HCF + STZ group demonstrated a significant reduction in serum glucose levels compared to the STZ-only group. Pro-inflammatory cytokines TNF-α and IL-1β were significantly decreased in HCF-treated diabetic rats, while the anti-inflammatory cytokine IL-10 was partially restored. Histopathological examination revealed severe pancreatic islet atrophy and renal degeneration in the diabetic group, which were markedly alleviated in the HCF + STZ group. These findings suggest that HCF’s immunomodulatory and anti-inflammatory properties may mitigate hyperglycemia and inflammatory responses in type 1 diabetes, warranting further investigation into its mechanisms and clinical applications.
{"title":"Protective effects of hydatid cyst fluid on inflammation and tissue damage in rat model of type 1 diabetes","authors":"Ehsan Ahmadpour , Kimia Moradi , Reyhaneh Moghaddami , Rafieh Bagherifar , Arshad Ghaffari-Nasab , Mahdi Mahdipour , Azadeh Mizani , Mahdi Ahmadi , Monir Khordadmehr , Mohammad Hasan Kohansal","doi":"10.1016/j.biocel.2025.106736","DOIUrl":"10.1016/j.biocel.2025.106736","url":null,"abstract":"<div><div>Cystic echinococcosis, caused by <em>Echinococcus granulosus</em>, is a zoonotic disease with immunomodulatory properties attributed to hydatid cyst fluid (HCF). Given the immune-modulating and anti-inflammatory properties of HCF observed in other contexts, its potential therapeutic effects in diabetes remain unexplored. This study aimed to investigate the potential therapeutic effects of HCF on glycemic control, inflammatory cytokines, and tissue histopathology in a streptozotocin (STZ)-induced model of type 1 diabetes. Twenty male rats were randomly divided into four groups (n = 5): a healthy control group, a hydatid cyst group that received three intraperitoneal injections of HCF at two-week intervals, a diabetic group that received a single intraperitoneal dose of STZ to induce diabetes, and a hydatid cyst + diabetic group (HCF + STZ) that received both HCF treatment and STZ administration. Serum glucose levels, inflammatory cytokines (TNF-α, IL-1β, and IL-10), and histopathological changes in pancreatic and renal tissues were analyzed. The HCF + STZ group demonstrated a significant reduction in serum glucose levels compared to the STZ-only group. Pro-inflammatory cytokines TNF-α and IL-1β were significantly decreased in HCF-treated diabetic rats, while the anti-inflammatory cytokine IL-10 was partially restored. Histopathological examination revealed severe pancreatic islet atrophy and renal degeneration in the diabetic group, which were markedly alleviated in the HCF + STZ group. These findings suggest that HCF’s immunomodulatory and anti-inflammatory properties may mitigate hyperglycemia and inflammatory responses in type 1 diabetes, warranting further investigation into its mechanisms and clinical applications.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106736"},"PeriodicalIF":3.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-healing wounds pose significant challenges and require effective therapeutic interventions. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in tissue regeneration. However, the functional differences between different subpopulations of EVs in wound healing remain understudied. This study aimed to evaluate the effects of two distinct subpopulations of clonal mesenchymal stromal cells (cMSC)-derived EVs (cMSC-EVs), namely 20 K and 110K-cMSC-EVs, primarily on in vitro wound healing process, providing fast and cost-effective alternatives to animal models.
Methods
In vitro assays were conducted to compare the effects of 20 K and 110K-cMSC-EVs, isolated through high-speed centrifugation and differential ultracentrifugation, respectively. For evaluation the main mechanisms of wound healing, including cell proliferation, cell migration, angiogenesis, and contraction. Human dermal fibroblasts (HDF) were considered as the main cells for analysis of these procedures. Moreover, gene expression analysis was performed to assess the impact of these EV subpopulations on the related process of wound healing on HDF.
Results
The results demonstrated that both 20 K and 110K-cMSC-EVs exhibited beneficial effects on cell proliferation, cell migration, angiogenesis, and gel contraction. RT-qPCR revealed that both EV types downregulated interleukin 6 (IL6), induced proliferation by upregulating proliferating cell nuclear antigen (PCNA), and regulated remodeling by upregulating matrix metallopeptidase 1 (MMP1) and downregulating collagen type 1 (COL1).
Discussion
This study highlights the effects of both 20 K and 110K-cMSC-EVs on the potency of HDFs in wound healing-related process. As the notable finding, 20K-cMSC-EVs offer a more feasible and cost-effective subpopulation for isolation and follow the GMP standard, recommended to utilize this fraction for therapeutic application.
{"title":"Comparative effects of various extracellular vesicle subpopulations derived from clonal mesenchymal stromal cells on cultured fibroblasts in wound healing-related process","authors":"Hedie Poorkazem , Maryam Saber , Azadeh Moradmand , Saeed Yakhkeshi , Homeyra Seydi , Ensiyeh Hajizadeh-Saffar , Faezeh Shekari , Seyedeh-Nafiseh Hassani","doi":"10.1016/j.biocel.2025.106737","DOIUrl":"10.1016/j.biocel.2025.106737","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-healing wounds pose significant challenges and require effective therapeutic interventions. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in tissue regeneration. However, the functional differences between different subpopulations of EVs in wound healing remain understudied. This study aimed to evaluate the effects of two distinct subpopulations of clonal mesenchymal stromal cells (cMSC)-derived EVs (cMSC-EVs), namely 20 K and 110K-cMSC-EVs, primarily on <em>in vitro</em> wound healing process, providing fast and cost-effective alternatives to animal models.</div></div><div><h3>Methods</h3><div>In vitro assays were conducted to compare the effects of 20 K and 110K-cMSC-EVs, isolated through high-speed centrifugation and differential ultracentrifugation, respectively. For evaluation the main mechanisms of wound healing, including cell proliferation, cell migration, angiogenesis, and contraction. Human dermal fibroblasts (HDF) were considered as the main cells for analysis of these procedures. Moreover, gene expression analysis was performed to assess the impact of these EV subpopulations on the related process of wound healing on HDF.</div></div><div><h3>Results</h3><div>The results demonstrated that both 20 K and 110K-cMSC-EVs exhibited beneficial effects on cell proliferation, cell migration, angiogenesis, and gel contraction. RT-qPCR revealed that both EV types downregulated interleukin 6 (<em>IL6</em>), induced proliferation by upregulating proliferating cell nuclear antigen <em>(PCNA)</em>, and regulated remodeling by upregulating matrix metallopeptidase 1 (<em>MMP1</em>) and downregulating collagen type 1 (<em>COL1</em>).</div></div><div><h3>Discussion</h3><div>This study highlights the effects of both 20 K and 110K-cMSC-EVs on the potency of HDFs in wound healing-related process. As the notable finding, 20K-cMSC-EVs offer a more feasible and cost-effective subpopulation for isolation and follow the GMP standard, recommended to utilize this fraction for therapeutic application.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106737"},"PeriodicalIF":3.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.biocel.2024.106703
Masahiro Yoshida , Romina Arzili , Marko Z. Nikolić
The importance of the crosstalk between lung epithelial and immune cells, which emerges from early development and lasts throughout life, is corroborated by a growing body of scientific evidence. This communication not only has a role in driving lung morphogenesis during development, but it is also required in adulthood for the maintenance of homeostasis and repair following infection or injury. Disruption of the intricate immune-epithelial crosstalk can lead to diseases such as COPD and IPF. In this review we summarise the current knowledge regarding the communication between various immune and epithelial cells in development, homeostasis, regeneration and disease, while identifying the current gaps in our knowledge required to facilitate the development of more effective therapies.
{"title":"Immune-epithelial cell interactions in lung development, homeostasis and disease","authors":"Masahiro Yoshida , Romina Arzili , Marko Z. Nikolić","doi":"10.1016/j.biocel.2024.106703","DOIUrl":"10.1016/j.biocel.2024.106703","url":null,"abstract":"<div><div>The importance of the crosstalk between lung epithelial and immune cells, which emerges from early development and lasts throughout life, is corroborated by a growing body of scientific evidence. This communication not only has a role in driving lung morphogenesis during development, but it is also required in adulthood for the maintenance of homeostasis and repair following infection or injury. Disruption of the intricate immune-epithelial crosstalk can lead to diseases such as COPD and IPF. In this review we summarise the current knowledge regarding the communication between various immune and epithelial cells in development, homeostasis, regeneration and disease, while identifying the current gaps in our knowledge required to facilitate the development of more effective therapies.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"178 ","pages":"Article 106703"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-11DOI: 10.1016/j.biocel.2024.106728
M. Ratnasingham, P. Bradding, K.M. Roach
Idiopathic pulmonary fibrosis (IPF) is a severe lung disease affecting around 5 million people globally, with a median survival of 3–4 years. Characterized by excessive scarring of lung tissue, IPF results from the accumulation of myofibroblasts that deposit extracellular matrix (ECM), causing fibrosis. Current treatments, pirfenidone and nintedanib, slow the disease but do not stop its progression. IPF pathogenesis involves repeated alveolar injury, leading to pro-fibrotic mediators like TGFβ1, which trigger fibroblast-to-myofibroblast transitions and ECM deposition.
Recent research suggests that transient receptor potential (TRP) channels, such as TRPV4, TRPC6, and TRPA1, play a key role in regulating calcium signalling and mechanical stress, crucial in myofibroblast activation.
Targeting TRP channels may disrupt fibrosis and offer new therapeutic strategies. Preclinical studies indicate that inhibiting TRP channels could reduce fibrosis, warranting further trials to explore their efficacy and safety in treating IPF and related fibrotic conditions
{"title":"The role of TRP channels in lung fibrosis: Mechanisms and therapeutic potential","authors":"M. Ratnasingham, P. Bradding, K.M. Roach","doi":"10.1016/j.biocel.2024.106728","DOIUrl":"10.1016/j.biocel.2024.106728","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a severe lung disease affecting around 5 million people globally, with a median survival of 3–4 years. Characterized by excessive scarring of lung tissue, IPF results from the accumulation of myofibroblasts that deposit extracellular matrix (ECM), causing fibrosis. Current treatments, pirfenidone and nintedanib, slow the disease but do not stop its progression. IPF pathogenesis involves repeated alveolar injury, leading to pro-fibrotic mediators like TGFβ1, which trigger fibroblast-to-myofibroblast transitions and ECM deposition.</div><div>Recent research suggests that transient receptor potential (TRP) channels, such as TRPV4, TRPC6, and TRPA1, play a key role in regulating calcium signalling and mechanical stress, crucial in myofibroblast activation.</div><div>Targeting TRP channels may disrupt fibrosis and offer new therapeutic strategies. Preclinical studies indicate that inhibiting TRP channels could reduce fibrosis, warranting further trials to explore their efficacy and safety in treating IPF and related fibrotic conditions</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106728"},"PeriodicalIF":3.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-29DOI: 10.1016/j.biocel.2024.106713
Yong-Zhen Li , Yuan Tian , Chen Yang , Yi-Fan Liu , Shun-Lin Qu , Liang Huang , Chi Zhang
Background
Type 2 diabetes (T2DM) is a chronic metabolic disorder characterized by insulin resistance and chronic inflammation. Adipose tissue macrophages (ATMs), central players in mediating pro-inflammatory responses within adipose tissue, have been shown to influence insulin sensitivity through exosome secretion. While the role of macrophages-derived exosomal miRNA has been studied in various diseases, their pathogenic roles in T2DM, particularly ATMs-derived exosomal miRNA in adipose tissue inflammation, remain underexplored.
Objectives
This study focuses specifically on T2DM, investigating the role of ATM-derived exosomal miRNAs in adipose tissue inflammation, a critical factor in the pathogenesis of T2DM.
Methods
ATM were isolated from visceral adipose tissues in patients with or without diabetes. Differentially expressed miRNAs in ATM-derived exosomes were predicted by high-throughput RNA sequencing. The RAW264.7 macrophages and 3T3-L1 preadipocytes was selected as a model system. Quantitative RT-PCR was used to assess miR-500a-5p expression. The direct binding of miR-500a-5p to Nrf2 mRNA 3′ UTR was verified by dual luciferase assay.
Results
MiR-500a-5p was also enriched in the exosomes of high-glucose-treated macrophages. Furthermore, these exosomes induced high expression of miR-500a-5p and activation of the NLRP3 inflammasome in adipocytes when co-cultured with them. Additionally, the reduction of miR-500a-5p expression in macrophages by using a miR-500a-5p inhibitor ameliorated the pro-inflammatory properties of the exosomes, and co-culturing these exosomes with adipocytes resulted in decreased expression of NLRP3 inflammasome-associated proteins in adipocytes. In contrast, induction of miR-500a-5p expression led to the opposite results. Moreover, the dual-luciferase assay confirmed that miR-500a-5p directly targeted the 3′ UTR of Nrf2 mRNA. Unlike miR-500a-5p, Nrf2 exhibited an anti-inflammatory response.
Conclusion
The results indicate that ATM-derived exosomal miR-500a-5p promotes NLRP3 inflammasome activation and adipose tissue inflammation through down-regulation of Nrf2 in adipocytes.
{"title":"Adipose tissue macrophages-derived exosomal MiR-500a-5p under high glucose promotes adipocytes inflammation by suppressing Nrf2 expression","authors":"Yong-Zhen Li , Yuan Tian , Chen Yang , Yi-Fan Liu , Shun-Lin Qu , Liang Huang , Chi Zhang","doi":"10.1016/j.biocel.2024.106713","DOIUrl":"10.1016/j.biocel.2024.106713","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes (T2DM) is a chronic metabolic disorder characterized by insulin resistance and chronic inflammation. Adipose tissue macrophages (ATMs), central players in mediating pro-inflammatory responses within adipose tissue, have been shown to influence insulin sensitivity through exosome secretion. While the role of macrophages-derived exosomal miRNA has been studied in various diseases, their pathogenic roles in T2DM, particularly ATMs-derived exosomal miRNA in adipose tissue inflammation, remain underexplored.</div></div><div><h3>Objectives</h3><div>This study focuses specifically on T2DM, investigating the role of ATM-derived exosomal miRNAs in adipose tissue inflammation, a critical factor in the pathogenesis of T2DM.</div></div><div><h3>Methods</h3><div>ATM were isolated from visceral adipose tissues in patients with or without diabetes. Differentially expressed miRNAs in ATM-derived exosomes were predicted by high-throughput RNA sequencing. The RAW264.7 macrophages and 3T3-L1 preadipocytes was selected as a model system. Quantitative RT-PCR was used to assess miR-500a-5p expression. The direct binding of miR-500a-5p to Nrf2 mRNA 3′ UTR was verified by dual luciferase assay.</div></div><div><h3>Results</h3><div>MiR-500a-5p was also enriched in the exosomes of high-glucose-treated macrophages. Furthermore, these exosomes induced high expression of miR-500a-5p and activation of the NLRP3 inflammasome in adipocytes when co-cultured with them. Additionally, the reduction of miR-500a-5p expression in macrophages by using a miR-500a-5p inhibitor ameliorated the pro-inflammatory properties of the exosomes, and co-culturing these exosomes with adipocytes resulted in decreased expression of NLRP3 inflammasome-associated proteins in adipocytes. In contrast, induction of miR-500a-5p expression led to the opposite results. Moreover, the dual-luciferase assay confirmed that miR-500a-5p directly targeted the 3′ UTR of Nrf2 mRNA. Unlike miR-500a-5p, Nrf2 exhibited an anti-inflammatory response.</div></div><div><h3>Conclusion</h3><div>The results indicate that ATM-derived exosomal miR-500a-5p promotes NLRP3 inflammasome activation and adipose tissue inflammation through down-regulation of Nrf2 in adipocytes.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"178 ","pages":"Article 106713"},"PeriodicalIF":3.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-28DOI: 10.1016/j.biocel.2024.106705
Meredith Hill , Sarah Stapleton , Phuong Thao Nguyen , Dayna Sais , Fiona Deutsch , Valerie C. Gay , Deborah J. Marsh , Nham Tran
MicroRNAs (miRNA,miRs) are small noncoding RNAs that are ubiquitously expressed in all mammalian cells. Their primary function is the regulation of nascent RNA transcripts by direct binding to regions on the target. There is now exciting data to suggest that these miRNAs can bind to other miRNAs, and this may have a broader impact on gene regulation in disease states. The oncomiR miR-21 is one of the highest-expressing miRNAs in cancer cells, and in this study, we characterise which miRNAs could be potential targets of miR-21. In cancer cells delivered with a miR-21 mimic, there was an observable shift of the miRNA milieu. We demonstrate that the miR-17–92a cluster, which harbours six miRNA members, may be a target for miR-21 regulation. Additionally, the primary transcript of miR-17–92a was reduced in the presence of miR-21. In the broader context of miR:miR regulation, overexpression of miR-21 shifted the expression of more than 150 miRNAs, including those known to regulate genes in cancer pathways such as the MAPK signalling and FoxO pathways. This study expands upon our limited understanding of miR:miR regulatory network and reinforces the concept that miRNAs can regulate each other, thereby influencing broader gene networks.
{"title":"The potential regulation of the miR-17–92a cluster by miR-21","authors":"Meredith Hill , Sarah Stapleton , Phuong Thao Nguyen , Dayna Sais , Fiona Deutsch , Valerie C. Gay , Deborah J. Marsh , Nham Tran","doi":"10.1016/j.biocel.2024.106705","DOIUrl":"10.1016/j.biocel.2024.106705","url":null,"abstract":"<div><div>MicroRNAs (miRNA,miRs) are small noncoding RNAs that are ubiquitously expressed in all mammalian cells. Their primary function is the regulation of nascent RNA transcripts by direct binding to regions on the target. There is now exciting data to suggest that these miRNAs can bind to other miRNAs, and this may have a broader impact on gene regulation in disease states. The oncomiR miR-21 is one of the highest-expressing miRNAs in cancer cells, and in this study, we characterise which miRNAs could be potential targets of miR-21. In cancer cells delivered with a miR-21 mimic, there was an observable shift of the miRNA milieu. We demonstrate that the miR-17–92a cluster, which harbours six miRNA members, may be a target for miR-21 regulation. Additionally, the primary transcript of miR-17–92a was reduced in the presence of miR-21. In the broader context of miR:miR regulation, overexpression of miR-21 shifted the expression of more than 150 miRNAs, including those known to regulate genes in cancer pathways such as the MAPK signalling and FoxO pathways. This study expands upon our limited understanding of miR:miR regulatory network and reinforces the concept that miRNAs can regulate each other, thereby influencing broader gene networks.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"178 ","pages":"Article 106705"},"PeriodicalIF":3.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号