Organophosphate pesticides (OPPs) are widely used chemical pesticides in all the developed countries. Among the OPPs, Chlorpyrifos (CPF) is predominantly used and has been linked to various adverse health effects from acute to chronic exposure. Exposure to pesticides both occupationally and environmentally causes frequent human health problems including neurological disorders, liver, kidney dysfunctions and cancer. The acute and chronic effects of these environmental toxicants have been linked to epigenetic changes that appear shortly after exposure, but can last for a lifetime and possibly be passed down through generations. The present study investigates the effects of acute and chronic exposure to CPF, the predominantly used OPP globally on human liver cells, focusing on the induction of DNA damage and epigenetic alterations. Human normal liver cells (WRL-68) were acutely and chronically exposed to varying concentrations of CPF. The results revealed significant DNA damage, epigenetic changes and the onset of neoplastic transformation as evidenced by alterations in the DNA repair genes, DNA methyltransferases markers, cell cycle markers, epithelial to mesenchymal transition markers (EMT) and loss of apoptosis. Additionally, chronic CPF exposure led to increased colony formation, proliferation and migratory properties of normal liver cells indicating the neoplastic transformation of these cells. These findings highlight the potential of CPF to disrupt the cellular integrity and promote carcinogenesis in the liver cells. The present study underscores the impact of chronic CPF exposure in the initiation of cancer and also highlights the importance of continued research to fully understand the chronic health implications of CPF, for developing targeted interventions to mitigate its carcinogenic risks.
有机磷农药(OPPs)是所有发达国家广泛使用的化学农药。在 OPPs 中,主要使用的是毒死蜱(CPF),它与从急性到慢性接触的各种不良健康影响有关。在职业和环境中接触杀虫剂会导致频繁的人类健康问题,包括神经系统疾病、肝脏和肾脏功能障碍以及癌症。这些环境毒物的急性和慢性影响与表观遗传学变化有关,这种变化在接触后不久就会出现,但可持续终生,并可能代代相传。本研究调查了急性和慢性接触氯化石蜡(全球主要使用的 OPP)对人类肝细胞的影响,重点是诱导 DNA 损伤和表观遗传学改变。人类正常肝细胞(WRL-68)急性和慢性暴露于不同浓度的氯化石蜡。结果显示,DNA 修复基因、DNA 甲基转移酶标记物、细胞周期标记物、上皮细胞向间充质转化标记物(EMT)的改变以及细胞凋亡的丧失证明了 DNA 损伤、表观遗传学改变和肿瘤转化的发生。此外,长期接触氯化石蜡会导致正常肝细胞的集落形成、增殖和迁移特性增加,表明这些细胞发生了肿瘤性转变。这些发现凸显了氯化石蜡破坏细胞完整性和促进肝细胞癌变的潜力。本研究强调了长期暴露于氯化石蜡对癌症发生的影响,同时也突出了继续研究以充分了解氯化石蜡对慢性健康的影响,从而制定有针对性的干预措施以降低其致癌风险的重要性。
{"title":"Toxicological Impact of Chronic Chlorpyrifos Exposure: DNA Damage and Epigenetic Alterations Induces Neoplastic Transformation of Liver Cells.","authors":"Pavithra Balakrishnan, Kishore Thirunavukarasu, Priyadharshini Tamizhmani, Antony Anista Michael, Thirunavukkarasu Velusamy","doi":"10.1016/j.bbrc.2025.151287","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151287","url":null,"abstract":"<p><p>Organophosphate pesticides (OPPs) are widely used chemical pesticides in all the developed countries. Among the OPPs, Chlorpyrifos (CPF) is predominantly used and has been linked to various adverse health effects from acute to chronic exposure. Exposure to pesticides both occupationally and environmentally causes frequent human health problems including neurological disorders, liver, kidney dysfunctions and cancer. The acute and chronic effects of these environmental toxicants have been linked to epigenetic changes that appear shortly after exposure, but can last for a lifetime and possibly be passed down through generations. The present study investigates the effects of acute and chronic exposure to CPF, the predominantly used OPP globally on human liver cells, focusing on the induction of DNA damage and epigenetic alterations. Human normal liver cells (WRL-68) were acutely and chronically exposed to varying concentrations of CPF. The results revealed significant DNA damage, epigenetic changes and the onset of neoplastic transformation as evidenced by alterations in the DNA repair genes, DNA methyltransferases markers, cell cycle markers, epithelial to mesenchymal transition markers (EMT) and loss of apoptosis. Additionally, chronic CPF exposure led to increased colony formation, proliferation and migratory properties of normal liver cells indicating the neoplastic transformation of these cells. These findings highlight the potential of CPF to disrupt the cellular integrity and promote carcinogenesis in the liver cells. The present study underscores the impact of chronic CPF exposure in the initiation of cancer and also highlights the importance of continued research to fully understand the chronic health implications of CPF, for developing targeted interventions to mitigate its carcinogenic risks.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"746 ","pages":"151287"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976783","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 : 2025-02-01Epub Date: 2025-01-03DOI: 10.1016/j.bbrc.2024.151241
Yutaro Fukushima, Asuka Kagami, Hirotaka Sonoda, Kotomi Shimokawa, Mary Ann Suico, Hirofumi Kai, Tsuyoshi Shuto
{"title":"Erratum to \"Dietary state and impact of DMSO on Caenorhabditis elegans aging: Insights from healthspan analysis\"[Biochem. Biophys. Res. Commun. (742),2025, 151156].","authors":"Yutaro Fukushima, Asuka Kagami, Hirotaka Sonoda, Kotomi Shimokawa, Mary Ann Suico, Hirofumi Kai, Tsuyoshi Shuto","doi":"10.1016/j.bbrc.2024.151241","DOIUrl":"10.1016/j.bbrc.2024.151241","url":null,"abstract":"","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":" ","pages":"151241"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926355","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 : 2025-01-23DOI: 10.1016/j.bbrc.2025.151361
Li Li, Yinyi Xiong, Wa Cao, Zhiyin Chen, Ling He, Mingfu Tong, Le Zhang, Moxin Wu
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors regret that after the publication of this article, they discovered that though they had observed that short-term treatment with EGFR inhibitors lapatinib and PD153035 could reduce liver fat accumulation, after long-term treatment, lipid accumulation still appeared in fatty liver accumulation, which is not significantly different from the model group. Therefore, they requested to withdraw the manuscript first to further clarify the pathogenesis of EGFR in fatty liver.
{"title":"Retraction notice to \"Epidermal growth factor receptor promotes high-fructose nonalcoholic fatty liver disease by inducing mitochondrial fission in zebrafish\" [Biochemical and Biophysical Research Communications 652 (2023) 112-120].","authors":"Li Li, Yinyi Xiong, Wa Cao, Zhiyin Chen, Ling He, Mingfu Tong, Le Zhang, Moxin Wu","doi":"10.1016/j.bbrc.2025.151361","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151361","url":null,"abstract":"<p><p>This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors regret that after the publication of this article, they discovered that though they had observed that short-term treatment with EGFR inhibitors lapatinib and PD153035 could reduce liver fat accumulation, after long-term treatment, lipid accumulation still appeared in fatty liver accumulation, which is not significantly different from the model group. Therefore, they requested to withdraw the manuscript first to further clarify the pathogenesis of EGFR in fatty liver.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":" ","pages":"151361"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036163","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 : 2025-01-23DOI: 10.1016/j.bbrc.2025.151385
Fen Wang, Wang Xiao, Jianwei Li, Zhixuan Zhang, Xiaodong Zhang, Jialong Sun, Yao Zhong, Xiaoyan Wang, Ruijuan Zhuang, Xin Gu
Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary vascular resistance and elevated pulmonary arterial pressure. Currently, pathogenesis of PAH remains poorly understood, and therapeutic options are limited. In this study, we aimed to explore role of p16INK4A (p16) in the development of PAH using mouse model induced by monocrotaline (MCT). We utilized p16 knockout mice to investigate protective effects on PAH pathophysiology. Histopathological analysis, Western blotting, and transcriptomic profiling revealed that p16 knockout significantly reduced pathological changes associated with MCT-induced PAH, including vascular remodeling and pulmonary fibrosis. These effects were correlated with enhanced autophagy and balanced oxidative stress response following p16 deletion. Transcriptome analysis indicated that the regulatory impact of p16 on autophagy and oxidative stress was primarily mediated through its modulation of oxidative phosphorylation and glutathione metabolic pathways. Our findings provide new insights in PAH pathogenesis and suggest that targeting p16 may offer novel therapeutic approach for treating PAH. These results highlighted that p16 could be a therapeutic target for modulating autophagy and oxidative stress in PAH, paving the way for future research in this area.
{"title":"p16<sup>INK4a</sup> promoted progress of MCT induced pulmonary hypertension via maintaining redox balance and autophagy pathway.","authors":"Fen Wang, Wang Xiao, Jianwei Li, Zhixuan Zhang, Xiaodong Zhang, Jialong Sun, Yao Zhong, Xiaoyan Wang, Ruijuan Zhuang, Xin Gu","doi":"10.1016/j.bbrc.2025.151385","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151385","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary vascular resistance and elevated pulmonary arterial pressure. Currently, pathogenesis of PAH remains poorly understood, and therapeutic options are limited. In this study, we aimed to explore role of p16INK4A (p16) in the development of PAH using mouse model induced by monocrotaline (MCT). We utilized p16 knockout mice to investigate protective effects on PAH pathophysiology. Histopathological analysis, Western blotting, and transcriptomic profiling revealed that p16 knockout significantly reduced pathological changes associated with MCT-induced PAH, including vascular remodeling and pulmonary fibrosis. These effects were correlated with enhanced autophagy and balanced oxidative stress response following p16 deletion. Transcriptome analysis indicated that the regulatory impact of p16 on autophagy and oxidative stress was primarily mediated through its modulation of oxidative phosphorylation and glutathione metabolic pathways. Our findings provide new insights in PAH pathogenesis and suggest that targeting p16 may offer novel therapeutic approach for treating PAH. These results highlighted that p16 could be a therapeutic target for modulating autophagy and oxidative stress in PAH, paving the way for future research in this area.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"151385"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045479","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 : 2025-01-23DOI: 10.1016/j.bbrc.2025.151384
Wang B Ben, Apaja M Pirjo
Ubiquitin-like autophagy-related gene ATG8 proteins are typically associated with degradative quality control via canonical double-membrane macro-autophagosomes in the cell. ATG8 proteins have now stepped forward in non-canonical pathways in single membrane organelles. The growing interest in non-canonical ATG8 roles has been stimulated by recent links to human conditions, especially in the regulation of inflammation, neurodegeneration and cancers. Here, we summarize the evidence linking non-canonical ATG8s to human pathologies and the quality control of acidic V-ATPase-regulated organelles in the cell.
{"title":"ATG8 in single membranes: Fresh players of endocytosis and acidic organelle quality control in cancer, neurodegeneration, and inflammation.","authors":"Wang B Ben, Apaja M Pirjo","doi":"10.1016/j.bbrc.2025.151384","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151384","url":null,"abstract":"<p><p>Ubiquitin-like autophagy-related gene ATG8 proteins are typically associated with degradative quality control via canonical double-membrane macro-autophagosomes in the cell. ATG8 proteins have now stepped forward in non-canonical pathways in single membrane organelles. The growing interest in non-canonical ATG8 roles has been stimulated by recent links to human conditions, especially in the regulation of inflammation, neurodegeneration and cancers. Here, we summarize the evidence linking non-canonical ATG8s to human pathologies and the quality control of acidic V-ATPase-regulated organelles in the cell.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"151384"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045540","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.bbrc.2025.151363
Wen-Wen Zhao, Yuan Gao, Yu-Ting Zhu, Fei-Liang Zhong, Xue-Gang Luo
In previous reports, we highlighted the significant involvement of SMYD3, a histone methyltransferase (HMT), in various aspects of cancer progression, including cell adhesion, migration, and invasion. In this study, we delved deeper into understanding the relationship between SMYD3 and epithelial-mesenchymal transition (EMT) both in cell lines and clinical samples. Our investigation uncovered a notable correlation between heightened SMYD3 expression and the presence of EMT markers in human breast cancer tissues. We found that the induction of SMYD3 expression is facilitated by transforming growth factor beta 1 (TGF-β1), which achieves this by suppressing miR-124, an inhibitor that targets SMYD3, through alterations in DNA methylation. Conversely, our experiments demonstrated that reducing SMYD3 levels through RNA interference impeded TGF-β1-induced EMT in breast cancer cells. Furthermore, our results revealed that SMYD3 alone has the capability to modulate the expression of markers associated with EMT. An intriguing aspect of our study is the revelation that SMYD3 influences the activation of vimentin by binding to its response elements within the core promoter region. Notably, this effect is independent of SMYD3's histone methyltransferase activity. These findings collectively underscore the pivotal role of SMYD3 in driving EMT, both in cell lines and primary cancer tissues, particularly emphasizing its significance in TGF-β1-induced EMT in breast cancer.
{"title":"SMYD3 plays a pivotal role in mediating the epithelial-mesenchymal transition process in breast cancer.","authors":"Wen-Wen Zhao, Yuan Gao, Yu-Ting Zhu, Fei-Liang Zhong, Xue-Gang Luo","doi":"10.1016/j.bbrc.2025.151363","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151363","url":null,"abstract":"<p><p>In previous reports, we highlighted the significant involvement of SMYD3, a histone methyltransferase (HMT), in various aspects of cancer progression, including cell adhesion, migration, and invasion. In this study, we delved deeper into understanding the relationship between SMYD3 and epithelial-mesenchymal transition (EMT) both in cell lines and clinical samples. Our investigation uncovered a notable correlation between heightened SMYD3 expression and the presence of EMT markers in human breast cancer tissues. We found that the induction of SMYD3 expression is facilitated by transforming growth factor beta 1 (TGF-β1), which achieves this by suppressing miR-124, an inhibitor that targets SMYD3, through alterations in DNA methylation. Conversely, our experiments demonstrated that reducing SMYD3 levels through RNA interference impeded TGF-β1-induced EMT in breast cancer cells. Furthermore, our results revealed that SMYD3 alone has the capability to modulate the expression of markers associated with EMT. An intriguing aspect of our study is the revelation that SMYD3 influences the activation of vimentin by binding to its response elements within the core promoter region. Notably, this effect is independent of SMYD3's histone methyltransferase activity. These findings collectively underscore the pivotal role of SMYD3 in driving EMT, both in cell lines and primary cancer tissues, particularly emphasizing its significance in TGF-β1-induced EMT in breast cancer.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"151363"},"PeriodicalIF":2.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045481","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.bbrc.2025.151372
Nuo Shen, Hao Sun, Guoqing Tu
Lung seven transmembrane receptor family is a small part of Arabidopsis gene family. So far, the function of some members of the this family is unknown. Plant elicitor peptide1 (Pep1) is one of damage-associated molecular patterns (DAMPs), which could trigger root growth inhibition and plant immunity responses. Here, we identified members of the Lung seven transmembrane family, and proved they are important for Pep1-induced root growth and development. We found that the expression levels of 7TM2 and 7TM6 were elevated in wild-type treated with Pep1. Phenotypic analysis showed that the growth phenotypes of 7tm2 and 7tm6 were similar to the wild-type under Pep1 treatment, but the 7tm2 7tm6 had a Pep1 hypersensitivity phenotype compared to wild-type. Furthermore, the complementation lines were able to restore the Pep1 phenotype of 7tm2 7tm6 to that similar to wild-type. These results suggest that 7TM2 and 7TM6 are involved in the regulation of root growth by Pep1. This study revealed the new functions of the Lung seven transmembrane receptor family and provided new ideas for further revealing the molecular mechanism of Pep1-regulated root growth and development.
{"title":"Lung seven transmembrane receptors are involved in Arabidopsis root growth mediated by Danger-associated peptide Pep1.","authors":"Nuo Shen, Hao Sun, Guoqing Tu","doi":"10.1016/j.bbrc.2025.151372","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151372","url":null,"abstract":"<p><p>Lung seven transmembrane receptor family is a small part of Arabidopsis gene family. So far, the function of some members of the this family is unknown. Plant elicitor peptide1 (Pep1) is one of damage-associated molecular patterns (DAMPs), which could trigger root growth inhibition and plant immunity responses. Here, we identified members of the Lung seven transmembrane family, and proved they are important for Pep1-induced root growth and development. We found that the expression levels of 7TM2 and 7TM6 were elevated in wild-type treated with Pep1. Phenotypic analysis showed that the growth phenotypes of 7tm2 and 7tm6 were similar to the wild-type under Pep1 treatment, but the 7tm2 7tm6 had a Pep1 hypersensitivity phenotype compared to wild-type. Furthermore, the complementation lines were able to restore the Pep1 phenotype of 7tm2 7tm6 to that similar to wild-type. These results suggest that 7TM2 and 7TM6 are involved in the regulation of root growth by Pep1. This study revealed the new functions of the Lung seven transmembrane receptor family and provided new ideas for further revealing the molecular mechanism of Pep1-regulated root growth and development.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"151372"},"PeriodicalIF":2.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036225","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 : 2025-01-20DOI: 10.1016/j.bbrc.2025.151346
Shayla R Fish, Catherine L Halley, Mythili Dileepan, Ann V Hertzel, Deborah M Dickey, David A Bernlohr
Adipose is a complex tissue comprised of adipocytes, immune cells, endothelial and progenitor stem cells. In humans, there are at least nine defined adipose depots, each containing variable numbers of genetically identified adipocyte clusters suggesting remarkable heterogeneity and potential functionality in each depot with respect to lipid metabolism. Although subcutaneous and visceral depots are commonly analyzed for biochemical and molecular functions, the mesenteric depot has been overlooked yet strongly implicated in lipid mediated immune surveillance. Since fatty acid binding proteins (FABPs) are primary cellular conduits to lipid trafficking, we evaluated the expression patterns for four major fatty acid binding proteins (FABP1, FABP3, FABP4 and FABP5) using a combination of gene expression, immunoblotting, and immunofluorescence in mesenteric fat from both young and old, male and female C57Bl/6J mice. All four FABPs were expressed at the mRNA and protein level in murine mesenteric adipose tissue. While there was no statistical change in expression of mesenteric FABP isoforms with sex or age, the expression of mesenteric FABP1 was increased, and FABP4 decreased, in both males and females as compared to perigonadal and inguinal depots. Surprisingly, immunofluorescence staining revealed that compared to subcutaneous or perigonadal depots, mesenteric fat expresses FABP3, but little FABP5, in adipocytes. These results highlight the diversity in adipose tissue and the importance of evaluating the mesenteric depot in the context of lipid transport and metabolism.
{"title":"Expression of fatty acid binding proteins in mesenteric adipose tissue.","authors":"Shayla R Fish, Catherine L Halley, Mythili Dileepan, Ann V Hertzel, Deborah M Dickey, David A Bernlohr","doi":"10.1016/j.bbrc.2025.151346","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151346","url":null,"abstract":"<p><p>Adipose is a complex tissue comprised of adipocytes, immune cells, endothelial and progenitor stem cells. In humans, there are at least nine defined adipose depots, each containing variable numbers of genetically identified adipocyte clusters suggesting remarkable heterogeneity and potential functionality in each depot with respect to lipid metabolism. Although subcutaneous and visceral depots are commonly analyzed for biochemical and molecular functions, the mesenteric depot has been overlooked yet strongly implicated in lipid mediated immune surveillance. Since fatty acid binding proteins (FABPs) are primary cellular conduits to lipid trafficking, we evaluated the expression patterns for four major fatty acid binding proteins (FABP1, FABP3, FABP4 and FABP5) using a combination of gene expression, immunoblotting, and immunofluorescence in mesenteric fat from both young and old, male and female C57Bl/6J mice. All four FABPs were expressed at the mRNA and protein level in murine mesenteric adipose tissue. While there was no statistical change in expression of mesenteric FABP isoforms with sex or age, the expression of mesenteric FABP1 was increased, and FABP4 decreased, in both males and females as compared to perigonadal and inguinal depots. Surprisingly, immunofluorescence staining revealed that compared to subcutaneous or perigonadal depots, mesenteric fat expresses FABP3, but little FABP5, in adipocytes. These results highlight the diversity in adipose tissue and the importance of evaluating the mesenteric depot in the context of lipid transport and metabolism.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"151346"},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036182","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}
C-type natriuretic peptide (CNP) can be a new disease-modifying anti-osteoarthritis drug (DMOAD) candidate because intraarticular injection of CNP attenuates both articular cartilage degradation and persistent pain in a rat knee arthritis model. This study aimed to elucidate the underlying molecular mechanisms by which CNP protects the knee joint from osteoarthritic changes. Gene expression analyses indicated that CNP did not interfere with the expression of IL1β -responsive genes in rat primary synovial fibroblasts or the monocytic cell line, RAW264.7 cells. In contrast, total RNA sequence analyses indicated that CNP negatively regulated the IL6-STAT3 signaling pathway and VEGFa gene expression in rat synovial fibroblasts. As previously indicated, IL6 induced phosphorylation of 705Tyr residue of STAT3 and its nuclear translocation to activate VEGFa gene expression; however, in this study, we showed that CNP induced phosphorylation of 727Ser residue and inhibited IL6-induced nuclear translocation of STAT3. Since the IL6 pathway has been shown to accelerate articular cartilage degradation and induce knee pain, our data suggest that CNP can act as a DMOAD by negatively regulating IL6-mediated proinflammatory signals in the knee joint.
{"title":"C-type natriuretic peptide suppresses VEGFa gene expression by attenuating IL6-STAT3 signal pathway in primary synovial fibroblasts from rat knee.","authors":"Riko Yamashita, Iori Nozawa, Shoichi Hasegawa, Yusuke Nakagawa, Kazumasa Miyatake, Hiroki Katagiri, Tomomasa Nakamura, Hideyuki Koga, Ichiro Sekiya, Toshitaka Yoshii, Kunikazu Tsuji","doi":"10.1016/j.bbrc.2025.151290","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151290","url":null,"abstract":"<p><p>C-type natriuretic peptide (CNP) can be a new disease-modifying anti-osteoarthritis drug (DMOAD) candidate because intraarticular injection of CNP attenuates both articular cartilage degradation and persistent pain in a rat knee arthritis model. This study aimed to elucidate the underlying molecular mechanisms by which CNP protects the knee joint from osteoarthritic changes. Gene expression analyses indicated that CNP did not interfere with the expression of IL1β -responsive genes in rat primary synovial fibroblasts or the monocytic cell line, RAW264.7 cells. In contrast, total RNA sequence analyses indicated that CNP negatively regulated the IL6-STAT3 signaling pathway and VEGFa gene expression in rat synovial fibroblasts. As previously indicated, IL6 induced phosphorylation of <sup>705</sup>Tyr residue of STAT3 and its nuclear translocation to activate VEGFa gene expression; however, in this study, we showed that CNP induced phosphorylation of <sup>727</sup>Ser residue and inhibited IL6-induced nuclear translocation of STAT3. Since the IL6 pathway has been shown to accelerate articular cartilage degradation and induce knee pain, our data suggest that CNP can act as a DMOAD by negatively regulating IL6-mediated proinflammatory signals in the knee joint.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"151290"},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036172","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}
People in Eastern Asia, including Japan, traditionally consume higher amounts of sodium chloride than in the United States and Western Europe, and it is common knowledge that impaired insulin secretion-rather than insulin resistance-is highly prevalent in Asian people who have diabetes mellitus. We previously reported that mice fed a high-fat and high-sodium chloride (HFHS) diet had a relatively lower degree of obesity than mice fed a high-fat diet, but had a comparatively impaired insulin secretion. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to dampen down the sympathetic nervous system, which reportedly is activated by a high-sodium chloride diet. In this study, we examined the effects of dapagliflozin, a SGLT2 inhibitor, on glucose metabolism and insulin secretion in mice fed a HFHS diet. C57BL6/J mice were fed a HFHS diet for 6 weeks and subsequently divided into two treatment groups fed: (1) a HFHS diet mixed with dapagliflozin for up to 3 weeks (HFHS + Da) and (2) a HFHS diet without dapagliflozin (HFHS). Dapagliflozin improved glucose tolerance and the insulinogenic index accompanied by increased pancreatic beta cell proliferation. Furthermore, dapagliflozin decreased both the tyrosine hydroxylase-positive area in pancreatic islets and catecholamine excretion in urine. Our results suggest that dapagliflozin improved insulin secretion by suppressing sympathetic nerve activation in mice fed a HFHS diet.
{"title":"Dapagliflozin increased pancreatic beta cell proliferation and insulinogenic index in mice fed a high-fat and high-sodium chloride diet.","authors":"Tomonori Hirose, Hiroshi Takagi, Mitsuhiro Kuno, Tomoyuki Sasaki, Keigo Taki, Yoshihiro Ito, Takashi Miyata, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Daisuke Hagiwara, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Hiroshi Arima","doi":"10.1016/j.bbrc.2025.151364","DOIUrl":"https://doi.org/10.1016/j.bbrc.2025.151364","url":null,"abstract":"<p><p>People in Eastern Asia, including Japan, traditionally consume higher amounts of sodium chloride than in the United States and Western Europe, and it is common knowledge that impaired insulin secretion-rather than insulin resistance-is highly prevalent in Asian people who have diabetes mellitus. We previously reported that mice fed a high-fat and high-sodium chloride (HFHS) diet had a relatively lower degree of obesity than mice fed a high-fat diet, but had a comparatively impaired insulin secretion. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to dampen down the sympathetic nervous system, which reportedly is activated by a high-sodium chloride diet. In this study, we examined the effects of dapagliflozin, a SGLT2 inhibitor, on glucose metabolism and insulin secretion in mice fed a HFHS diet. C57BL6/J mice were fed a HFHS diet for 6 weeks and subsequently divided into two treatment groups fed: (1) a HFHS diet mixed with dapagliflozin for up to 3 weeks (HFHS + Da) and (2) a HFHS diet without dapagliflozin (HFHS). Dapagliflozin improved glucose tolerance and the insulinogenic index accompanied by increased pancreatic beta cell proliferation. Furthermore, dapagliflozin decreased both the tyrosine hydroxylase-positive area in pancreatic islets and catecholamine excretion in urine. Our results suggest that dapagliflozin improved insulin secretion by suppressing sympathetic nerve activation in mice fed a HFHS diet.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"151364"},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036176","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}