Pub Date : 2025-02-24DOI: 10.1016/j.yexcr.2025.114480
James Jack Willis Hucklesby , Catherine Elizabeth Angel , Euan Scott Graham , Peter Rod Dunbar , Nigel Peter Birch , Evert Jan Loef
CCL21 is a key homeostatic chemokine best known for its role in lymphocyte homing and compartmentalization in the lymph node. CCL21 also plays a role in trans-endothelial migration and is known to be bound to the surface of endothelial cells in high endothelial venules and inflamed tissues. The effects of CCL21 are highly dependent on its form; full-length CCL21 can bind to the surface of endothelial cells and induce lymphocyte arrest and transendothelial migration, whereas truncated CCL21 cannot. Earlier literature indicates that plasmin can cleave CCL21 from the surface of immune cells, although the mechanism regulating this process on endothelial cells has not been studied.
This study demonstrates that the human endothelial-like cell lines ECV304 (LS12) and HMEC-1 can bind the plasmin precursor plasminogen to their cell surface. Furthermore, ECV304 (LS12) cells could endogenously activate plasminogen, yielding plasmin that subsequently released cell surface CCL21. In contrast, cell-surface CCL21 was only released from HMEC-1 after exogenous tPA activated the surface-bound plasminogen. Finally, it was shown that plasmin reduced T cell adhesion to endothelial-like cells with cell surface CCL21 under shear stress conditions.
Collectively, for the first time, these data demonstrate that plasmin can cleave endothelial cell surface CCL21, reducing T cell adhesion to endothelial cells under shear stress. Interestingly, this study also indicates that endothelial cells’ differential expression of plasminogen activators may regulate plasmin availability and influence T-cell arrest.
{"title":"Plasmin reduces human T cell arrest on endothelial-like cells by cleaving bound CCL21 from the cell surface","authors":"James Jack Willis Hucklesby , Catherine Elizabeth Angel , Euan Scott Graham , Peter Rod Dunbar , Nigel Peter Birch , Evert Jan Loef","doi":"10.1016/j.yexcr.2025.114480","DOIUrl":"10.1016/j.yexcr.2025.114480","url":null,"abstract":"<div><div>CCL21 is a key homeostatic chemokine best known for its role in lymphocyte homing and compartmentalization in the lymph node. CCL21 also plays a role in trans-endothelial migration and is known to be bound to the surface of endothelial cells in high endothelial venules and inflamed tissues. The effects of CCL21 are highly dependent on its form; full-length CCL21 can bind to the surface of endothelial cells and induce lymphocyte arrest and transendothelial migration, whereas truncated CCL21 cannot. Earlier literature indicates that plasmin can cleave CCL21 from the surface of immune cells, although the mechanism regulating this process on endothelial cells has not been studied.</div><div>This study demonstrates that the human endothelial-like cell lines ECV304 (LS12) and HMEC-1 can bind the plasmin precursor plasminogen to their cell surface. Furthermore, ECV304 (LS12) cells could endogenously activate plasminogen, yielding plasmin that subsequently released cell surface CCL21. In contrast, cell-surface CCL21 was only released from HMEC-1 after exogenous tPA activated the surface-bound plasminogen. Finally, it was shown that plasmin reduced T cell adhesion to endothelial-like cells with cell surface CCL21 under shear stress conditions.</div><div>Collectively, for the first time, these data demonstrate that plasmin can cleave endothelial cell surface CCL21, reducing T cell adhesion to endothelial cells under shear stress. Interestingly, this study also indicates that endothelial cells’ differential expression of plasminogen activators may regulate plasmin availability and influence T-cell arrest.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114480"},"PeriodicalIF":3.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515220","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 : 2025-02-22DOI: 10.1016/j.yexcr.2025.114474
Wang Huimin , Wu Xin , Yu Shan , Zhang Junwang , Wen Jing , Wang Yuan , Liu Qingtong , Li Xiaohui , Yao Jia , Yuan Lili
Elevated lactate levels increase the risk of liver cancer progression. However, the mechanisms by which lactate promotes liver cancer progression remain poorly understood. Epithelial-mesenchymal transition (EMT), characterized by the loss of epithelial cells polarity and cell-cell adhesion, leading to the acquisition of mesenchymal-like phenotypes, is widely recognized as a key contributor to liver cancer progression. TWIST1 (Twist Family BHLH Transcription Factor 1) plays a central role in inducing EMT. Here, we investigated the role of lactate in promoting EMT in liver cancer and the underlying regulatory mechanisms. High levels of lactate significantly promoted EMT progression in liver cancer cells. Mechanistically, lactate-induced lactylation of TWIST1 in vivo and in vitro. Mutation assay confirmed that Lysine 33 (K33) is the major site of TWIST1 lactylation. Moreover, cell fractionation & luciferase reporter assay results identified that TWIST1-K33R mutant impaired the EMT process via inhibiting nuclear import and the transcriptional activity. Thus, our findings provide novel insights into the regulatory role of lactate in EMT in liver cancer pathogenesis. Additionally, targeting of lactate-driven lactylation of TWIST1 may boost the therapeutic strategy for liver cancer.
{"title":"Lactate promotes the epithelial-mesenchymal transition of liver cancer cells via TWIST1 lactylation","authors":"Wang Huimin , Wu Xin , Yu Shan , Zhang Junwang , Wen Jing , Wang Yuan , Liu Qingtong , Li Xiaohui , Yao Jia , Yuan Lili","doi":"10.1016/j.yexcr.2025.114474","DOIUrl":"10.1016/j.yexcr.2025.114474","url":null,"abstract":"<div><div>Elevated lactate levels increase the risk of liver cancer progression. However, the mechanisms by which lactate promotes liver cancer progression remain poorly understood. Epithelial-mesenchymal transition (EMT), characterized by the loss of epithelial cells polarity and cell-cell adhesion, leading to the acquisition of mesenchymal-like phenotypes, is widely recognized as a key contributor to liver cancer progression. TWIST1 (Twist Family BHLH Transcription Factor 1) plays a central role in inducing EMT. Here, we investigated the role of lactate in promoting EMT in liver cancer and the underlying regulatory mechanisms. High levels of lactate significantly promoted EMT progression in liver cancer cells. Mechanistically, lactate-induced lactylation of TWIST1 <em>in vivo</em> and <em>in vitro</em>. Mutation assay confirmed that Lysine 33 (K33) is the major site of TWIST1 lactylation. Moreover, cell fractionation & luciferase reporter assay results identified that TWIST1-K33R mutant impaired the EMT process via inhibiting nuclear import and the transcriptional activity. Thus, our findings provide novel insights into the regulatory role of lactate in EMT in liver cancer pathogenesis. Additionally, targeting of lactate-driven lactylation of TWIST1 may boost the therapeutic strategy for liver cancer.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114474"},"PeriodicalIF":3.3,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491444","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 : 2025-02-21DOI: 10.1016/j.yexcr.2025.114461
Ning Ma , Lei Huang , Qianxu Zhou , Xiaomei Zhang , Qing Luo , Guanbin Song
Mesenchymal stem cells (MSCs) have self-renewal ability and the potential for multi-directional differentiation, and their clinical application has promising prospects, but improving the migration ability of MSCs in vivo is one of the challenges. We previously determined mechanical stretch at 1 Hz with 10 % strain for 8 h can significantly promote MSC migration, however, the molecular mechanism remains poorly understood. Here, we reported that the expression and activity of yes-associated protein (YAP) are upregulated after mechanical stretch. As a classical inhibitor of the YAP-TEAD activity and YAP protein, the treatment of verteporfin (VP) suppressed mechanical stretch-promoted MSC migration. We also observed F-actin polymerization after mechanical stretch. Next, we used Latrunculin A (Lat A), the most widely used reagent to depolymerize actin filaments, to treat MSCs and we found that Lat A treatment inhibits MSC migration by suppressing YAP expression and activity. In addition, the protein expression of Piezo1 was also upregulated after mechanical stretch. Knockdown of Piezo1 suppressed mechanical stretch-promoted MSC migration by restraining F-actin polymerization. Together, these findings demonstrate the role of Piezo1/F-actin/YAP signaling pathway in MSC migration under mechanical stretch, providing new experimental evidence for an in-depth understanding the mechanobiological mechanism of MSC migration.
{"title":"Mechanical stretch promotes the migration of mesenchymal stem cells via Piezo1/F-actin/YAP axis","authors":"Ning Ma , Lei Huang , Qianxu Zhou , Xiaomei Zhang , Qing Luo , Guanbin Song","doi":"10.1016/j.yexcr.2025.114461","DOIUrl":"10.1016/j.yexcr.2025.114461","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) have self-renewal ability and the potential for multi-directional differentiation, and their clinical application has promising prospects, but improving the migration ability of MSCs <em>in vivo</em> is one of the challenges. We previously determined mechanical stretch at 1 Hz with 10 % strain for 8 h can significantly promote MSC migration, however, the molecular mechanism remains poorly understood. Here, we reported that the expression and activity of yes-associated protein (YAP) are upregulated after mechanical stretch. As a classical inhibitor of the YAP-TEAD activity and YAP protein, the treatment of verteporfin (VP) suppressed mechanical stretch-promoted MSC migration. We also observed F-actin polymerization after mechanical stretch. Next, we used Latrunculin A (Lat A), the most widely used reagent to depolymerize actin filaments, to treat MSCs and we found that Lat A treatment inhibits MSC migration by suppressing YAP expression and activity. In addition, the protein expression of Piezo1 was also upregulated after mechanical stretch. Knockdown of Piezo1 suppressed mechanical stretch-promoted MSC migration by restraining F-actin polymerization. Together, these findings demonstrate the role of Piezo1/F-actin/YAP signaling pathway in MSC migration under mechanical stretch, providing new experimental evidence for an in-depth understanding the mechanobiological mechanism of MSC migration.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114461"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474052","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 : 2025-02-21DOI: 10.1016/j.yexcr.2025.114452
Md. Kaykobad Hossain , Lucas Unger , Ulrik Larsen , Altanchimeg Altankhuyag , Thomas Aga Legøy , Joao A. Paulo , Heidrun Vethe , Luiza Ghila
Characterizing the initial stages of oncogenic transformation allows the identification of tumor-promoting processes before the inherent clonal selection of the aggressive clones. Here, we used global proteomics, genetic cell tracing, and immunofluorescence to dynamically map the very early stages of cancer initiation in a mouse model of bladder cancer. We observed a very rapid and incremental proteome dysregulation, with changes in the energy metabolism, proliferation and immune signatures dominating the landscape. The changes in the lipid metabolism were immediate and defined by an increase fatty acid metabolism and lipid transport, followed by the activation of the immune landscape. Alongside the changes in the immune signature and lipid metabolism, we also mapped a clear increase in the cell cycle-related pathways and proliferation. Proliferation was mainly restricted to the basal epithelial layer rapidly leading to urothelium thickening, despite the progressive loss of the superficial layer. Moreover, we observed a tilt in the energy balance towards increased glucose metabolism, probably characterizing cells of the tumor microenvironment. All of the observed proteome signature changes were persistent, being retained and sometimes intensified or diversified along the timeline. The signatures observed in this pilot suggest these processes as potentially targetable drivers of the future neoplastic transformations in the bladder.
{"title":"Mapping the initial effects of carcinogen-induced oncogenic transformation in the mouse bladder","authors":"Md. Kaykobad Hossain , Lucas Unger , Ulrik Larsen , Altanchimeg Altankhuyag , Thomas Aga Legøy , Joao A. Paulo , Heidrun Vethe , Luiza Ghila","doi":"10.1016/j.yexcr.2025.114452","DOIUrl":"10.1016/j.yexcr.2025.114452","url":null,"abstract":"<div><div>Characterizing the initial stages of oncogenic transformation allows the identification of tumor-promoting processes before the inherent clonal selection of the aggressive clones. Here, we used global proteomics, genetic cell tracing, and immunofluorescence to dynamically map the very early stages of cancer initiation in a mouse model of bladder cancer. We observed a very rapid and incremental proteome dysregulation, with changes in the energy metabolism, proliferation and immune signatures dominating the landscape. The changes in the lipid metabolism were immediate and defined by an increase fatty acid metabolism and lipid transport, followed by the activation of the immune landscape. Alongside the changes in the immune signature and lipid metabolism, we also mapped a clear increase in the cell cycle-related pathways and proliferation. Proliferation was mainly restricted to the basal epithelial layer rapidly leading to urothelium thickening, despite the progressive loss of the superficial layer. Moreover, we observed a tilt in the energy balance towards increased glucose metabolism, probably characterizing cells of the tumor microenvironment. All of the observed proteome signature changes were persistent, being retained and sometimes intensified or diversified along the timeline. The signatures observed in this pilot suggest these processes as potentially targetable drivers of the future neoplastic transformations in the bladder.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114452"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474559","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 : 2025-02-21DOI: 10.1016/j.yexcr.2025.114477
Yutong Guo , Hanzhang Zhou , Yixiang Wang , Yan Gu
Bone marrow (BM) of postmenopausal osteoporosis has been found highly inflammatory, resulting from dysregulated immune cells induced by both estrogen efficiency and body aging. NETosis of neutrophils has been found aberrantly activated in age-related chronic inflammation, while their role in postmenopausal osteoporosis remains unclear. Here we found NETosis of BM neutrophils of OVX (ovariectomy) mice was significantly activated, and we verified NETs released by neutrophils induced M1 polarization and osteoclastogenesis of RAW264.7 macrophages. Further, we demonstrated effects of NETs on osteoclastogenesis was mediated by cGAS-STING/AKT2 pathway. Finally, we found in vivo NETs-clearance through GSK484 significantly inhibited osteoclastogenesis and attenuated osteoporosis of OVX mice. Our study highlights the role of neutrophil NETosis in activating osteoclastogenesis and bone resorption of postmenopausal osteoporosis, thereby providing novel targets for bone loss treatment.
{"title":"Activated NETosis of bone marrow neutrophils up-regulates macrophage osteoclastogenesis via cGAS-STING/AKT2 pathway to promote osteoporosis","authors":"Yutong Guo , Hanzhang Zhou , Yixiang Wang , Yan Gu","doi":"10.1016/j.yexcr.2025.114477","DOIUrl":"10.1016/j.yexcr.2025.114477","url":null,"abstract":"<div><div>Bone marrow (BM) of postmenopausal osteoporosis has been found highly inflammatory, resulting from dysregulated immune cells induced by both estrogen efficiency and body aging. NETosis of neutrophils has been found aberrantly activated in age-related chronic inflammation, while their role in postmenopausal osteoporosis remains unclear. Here we found NETosis of BM neutrophils of OVX (ovariectomy) mice was significantly activated, and we verified NETs released by neutrophils induced M1 polarization and osteoclastogenesis of RAW264.7 macrophages. Further, we demonstrated effects of NETs on osteoclastogenesis was mediated by cGAS-STING/AKT2 pathway. Finally, we found <em>in vivo</em> NETs-clearance through GSK484 significantly inhibited osteoclastogenesis and attenuated osteoporosis of OVX mice. Our study highlights the role of neutrophil NETosis in activating osteoclastogenesis and bone resorption of postmenopausal osteoporosis, thereby providing novel targets for bone loss treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114477"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482569","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 : 2025-02-21DOI: 10.1016/j.yexcr.2025.114447
Ji-Long Liu (Editor-in-Chief)
{"title":"Epic, classic, and remarkable: 75 years of Experimental Cell Research","authors":"Ji-Long Liu (Editor-in-Chief)","doi":"10.1016/j.yexcr.2025.114447","DOIUrl":"10.1016/j.yexcr.2025.114447","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114447"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482570","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}
Background: Cellular senescence refers to a condition where cells permanently cease division while maintaining metabolic activity. Doxorubicin (Dox) is known as an agent of induction of cellular senescence. This study aimed to explore the potential role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) in mitigating Dox induced senescent.
Method: NIH3T3 cells were treated by various concentrations of Dox with or without hucMSC-Exo, cell morphology, viability, migration, senescence-associated SA-β-Gal staining were monitored. Cellular senescence was induced in C57BL/6J mice via administration of 5 mg/kg Doxorubicin, followed by treatment with hucMSC-Exo or metformin. Assessments included body weight, liver and kidney weight, colon length, SA-β-Gal staining of kidney and skin, molecular biomarkers of aging such as p16INK4A, p53, and p21Waf1/Clip1 to evaluate senescence status.
Result: We found that after the treatment of exosomes or metformin improved several aging-related phenotypes in both mouse and cellular models, including increases in body weight, liver and kidney weights, and the reduction of SA-β-Gal positive cells in kidney and skin tissues as well as cell models. At the molecular level, hucMSC-Exo resulted in the downregulation of inflammatory factors and senescence markers in liver and kidney tissues as well as cell models.
Conclusion: Our study demonstrates hucMSC-Exo may ameliorate Dox induced senescence either in NIH3T3 cells or in mice.
{"title":"Human umbilical cord mesenchymal stem cell-derived exosome ameliorate doxorubicin-induced senescence.","authors":"Zhen Yang, Feng Yan, Jiangwei Yuan, Manjun Yang, Jinyu Wang, Changqiao You, Kaiqun Ren","doi":"10.1016/j.yexcr.2025.114450","DOIUrl":"10.1016/j.yexcr.2025.114450","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence refers to a condition where cells permanently cease division while maintaining metabolic activity. Doxorubicin (Dox) is known as an agent of induction of cellular senescence. This study aimed to explore the potential role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) in mitigating Dox induced senescent.</p><p><strong>Method: </strong>NIH3T3 cells were treated by various concentrations of Dox with or without hucMSC-Exo, cell morphology, viability, migration, senescence-associated SA-β-Gal staining were monitored. Cellular senescence was induced in C57BL/6J mice via administration of 5 mg/kg Doxorubicin, followed by treatment with hucMSC-Exo or metformin. Assessments included body weight, liver and kidney weight, colon length, SA-β-Gal staining of kidney and skin, molecular biomarkers of aging such as p16<sup>INK4A</sup>, p53, and p21<sup>Waf1/Clip1</sup> to evaluate senescence status.</p><p><strong>Result: </strong>We found that after the treatment of exosomes or metformin improved several aging-related phenotypes in both mouse and cellular models, including increases in body weight, liver and kidney weights, and the reduction of SA-β-Gal positive cells in kidney and skin tissues as well as cell models. At the molecular level, hucMSC-Exo resulted in the downregulation of inflammatory factors and senescence markers in liver and kidney tissues as well as cell models.</p><p><strong>Conclusion: </strong>Our study demonstrates hucMSC-Exo may ameliorate Dox induced senescence either in NIH3T3 cells or in mice.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114450"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482571","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 : 2025-02-20DOI: 10.1016/j.yexcr.2025.114456
Long Peng , Yanting Luo , Fang Tan , Qian Chen , Jiafu Wang , Xiaolan Ouyang , Bingyuan Wu , Xixiang Tang , Suhua Li
Contrast-induced acute kidney injury (CIAKI) is a common complication after contrast media administration. Growing evidences implicate microRNA (miR)-30c has a key role in renal diseases. This study aimed to investigate the role and mechanism of miR-30c in CIAKI. CIAKI rat models were established using tail vein injection of omnipaque. MiR-30c was significantly downregulated in CIAKI models both in vivo and in vitro, concomitant with increased cell apoptosis and deteriorated renal injury. Meanwhile, the cell apoptosis, renal dysfunction and renal injury under contrast exposure were alleviated after overexpression of miR-30c. Mechanistically, we demonstrated that miR-30c directly targeted SOCS1, whose downregulation reduced contrast-induced HK-2 cell apoptosis. Furthermore, the upregulation of SOCS1 abolish the protective effect of the overexpression of miR-30c on contrast-induced cell apoptosis. In summary, overexpression of miR-30c inhibited renal tubular epithelial cell apoptosis and mitigated CIAKI via inhibiting the gene of SOCS1.
{"title":"microRNA-30c attenuates contrast-induced acute kidney injury by reducing renal tubular epithelial cell apoptosis via targeting SOCS1","authors":"Long Peng , Yanting Luo , Fang Tan , Qian Chen , Jiafu Wang , Xiaolan Ouyang , Bingyuan Wu , Xixiang Tang , Suhua Li","doi":"10.1016/j.yexcr.2025.114456","DOIUrl":"10.1016/j.yexcr.2025.114456","url":null,"abstract":"<div><div>Contrast-induced acute kidney injury (CIAKI) is a common complication after contrast media administration. Growing evidences implicate microRNA (miR)-30c has a key role in renal diseases. This study aimed to investigate the role and mechanism of miR-30c in CIAKI. CIAKI rat models were established using tail vein injection of omnipaque. MiR-30c was significantly downregulated in CIAKI models both in vivo and in vitro, concomitant with increased cell apoptosis and deteriorated renal injury. Meanwhile, the cell apoptosis, renal dysfunction and renal injury under contrast exposure were alleviated after overexpression of miR-30c. Mechanistically, we demonstrated that miR-30c directly targeted SOCS1, whose downregulation reduced contrast-induced HK-2 cell apoptosis. Furthermore, the upregulation of SOCS1 abolish the protective effect of the overexpression of miR-30c on contrast-induced cell apoptosis. In summary, overexpression of miR-30c inhibited renal tubular epithelial cell apoptosis and mitigated CIAKI via inhibiting the gene of SOCS1.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114456"},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476027","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 : 2025-02-20DOI: 10.1016/j.yexcr.2025.114460
Pooja Rai , Rakesh Kumar
H50Q mutations in the SNCA gene, also known as also known as the alpha-Synuclein (α-Syn), have been causally linked to familial Parkinson's disease (PD). PD is primarily characterized by the progressive loss of dopaminergic neurons in the substantia nigra region of the brain.α-Syn- plays a pivotal role in the formation of Lewy bodies (LB), a prominent pathological marker in PD. Growing evidence has highlighted the involvement of the insulin signaling pathway dysfunction in various neurodegenerative models. This study aimed to explore how the H50Q mutation in α-Syn influences the insulin signaling pathway and the overall lifespan of fruit flies afflicted with PD. It has been established that a mutation in α-Syn affects mitochondrial function and increases oxidative stress, ultimately contributing to the death of dopaminergic neurons. The impairment of mitochondrial function disrupts metabolism and exerts an adverse effect on the insulin signaling pathway. Furthermore, the unfolded protein response of the endoplasmic reticulum (ER) are investigated and observed a decrease in the expression of PERK (Protein kinase R-like ER kinase) during ER stress. These findings confirm the intricate interplay between the insulin signaling pathway and the activation of the PERK-ER stress pathway. However, the degeneration of neurons triggers a neuroinflammatory response, which are found to be mitigated by the improvement of insulin signaling and the PERK-ER stress-related pathway. The results of this studyshed light on the novel regulatory role of PERK within the insulin signaling pathway and suggest its potential as a therapeutic candidate for modulating neuroinflammation in the context of α-Syn -associated PD pathology.
{"title":"H50Q mutation in alpha-Synuclein impairs the insulin signaling pathway and induces neuroinflammation in the Drosophila model","authors":"Pooja Rai , Rakesh Kumar","doi":"10.1016/j.yexcr.2025.114460","DOIUrl":"10.1016/j.yexcr.2025.114460","url":null,"abstract":"<div><div>H50Q mutations in the SNCA gene, also known as also known as the <em>alpha-Synuclein</em> (α-<em>Syn</em>), have been causally linked to familial Parkinson's disease (PD). PD is primarily characterized by the progressive loss of dopaminergic neurons in the substantia nigra region of the brain.α-Syn- plays a pivotal role in the formation of Lewy bodies (LB), a prominent pathological marker in PD. Growing evidence has highlighted the involvement of the insulin signaling pathway dysfunction in various neurodegenerative models. This study aimed to explore how the H50Q mutation in α-<em>Syn</em> influences the insulin signaling pathway and the overall lifespan of fruit flies afflicted with PD. It has been established that a mutation in α-<em>Syn</em> affects mitochondrial function and increases oxidative stress, ultimately contributing to the death of dopaminergic neurons. The impairment of mitochondrial function disrupts metabolism and exerts an adverse effect on the insulin signaling pathway. Furthermore, the unfolded protein response of the endoplasmic reticulum (ER) are investigated and observed a decrease in the expression of PERK (Protein kinase R-like ER kinase) during ER stress. These findings confirm the intricate interplay between the insulin signaling pathway and the activation of the PERK-ER stress pathway. However, the degeneration of neurons triggers a neuroinflammatory response, which are found to be mitigated by the improvement of insulin signaling and the PERK-ER stress-related pathway. The results of this studyshed light on the novel regulatory role of PERK within the insulin signaling pathway and suggest its potential as a therapeutic candidate for modulating neuroinflammation in the context of α-Syn -associated PD pathology.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114460"},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476042","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 : 2025-02-20DOI: 10.1016/j.yexcr.2025.114457
Daodi Qiu , Binghan Yan , Haipeng Xue , Zhanwang Xu , Guoqing Tan , Yajuan Liu
Bone metabolic disorders, constituting a group of prevalent and grave conditions, currently have a scarcity of therapeutic alternatives. Over the recent past, exosomes have been at the forefront of research interest, owing to their nanoparticulate nature and potential for therapeutic intervention. ncRNAs are a class of heterogeneous transcripts that they lack protein-encoding capacity, yet they can modulate the expression of other genes through multiple mechanisms. Mounting evidence underscores the intricate role of exosomes as ncRNAs couriers implicated in the pathogenesis of bone metabolic disorders. In this review, we endeavor to elucidate recent insights into the roles of three ncRNAs – miRNAs, lncRNAs, and circRNAs – in bone metabolic ailments such as osteoporosis, osteoarthritis, and rheumatoid arthritis. Additionally, we examine the viability of exosomal ncRNAs as innovative, cell-free modalities in the diagnosis and therapeutic management of bone metabolic disorders. We aim to uncover the critical function of exosomal ncRNAs within the context of bone metabolic diseases.
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