{"title":"HBV感染肝细胞携带OCT4/miR-1246/β-catenin外泌体加速肝纤维化","authors":"Tiantian Zhu, Yuankun Chen, Mingyue Niu, Qionghan He, Minhua Weng, Zheng Wang, Wenting Li","doi":"10.1002/jbt.70521","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Accumulating research highlights the critical involvement of octamer-binding transcription factor 4 (OCT4) in liver fibrosis (LF) development. However, the mechanistic relationship between OCT4 and hepatitis B virus (HBV)-associated LF remains unclear. HBV exposure markedly upregulated OCT4 and miR-1246 expression in both HepAD38 and HepG2-NTCP cell lines. These effects were reversed by entecavir treatment or the Hepatitis B X (HBx) knockdown. Furthermore, overexpression of OCT4 enhanced expression of miR-1246, β-catenin, and LF-associated genes in LX2 (Hepatic stellate cell) cells. Interestingly, exosomes from HBV infected HepG2-NTCP cells upregulated OCT4/miR-1246/β-catenin expression as well as α-SMA, Col1A and TIMP-1 in LX2 cells. These fibrogenic effects were inhibited by HBx gRNA. Moreover, 26 HBV infected patients were enrolled in this study. The expression of miR-1246 and β-catenin in liver tissue were strongly correlated with LF. These results showed that HBV induced LF through exosomal OCT4/miR-1246/β-catenin Pathway, which lay a basis for LF treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exosome Carrying OCT4/miR-1246/β-catenin Deriving From HBV Infected Hepatocytes Accelerated Liver Fibrosis\",\"authors\":\"Tiantian Zhu, Yuankun Chen, Mingyue Niu, Qionghan He, Minhua Weng, Zheng Wang, Wenting Li\",\"doi\":\"10.1002/jbt.70521\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Accumulating research highlights the critical involvement of octamer-binding transcription factor 4 (OCT4) in liver fibrosis (LF) development. However, the mechanistic relationship between OCT4 and hepatitis B virus (HBV)-associated LF remains unclear. HBV exposure markedly upregulated OCT4 and miR-1246 expression in both HepAD38 and HepG2-NTCP cell lines. These effects were reversed by entecavir treatment or the Hepatitis B X (HBx) knockdown. Furthermore, overexpression of OCT4 enhanced expression of miR-1246, β-catenin, and LF-associated genes in LX2 (Hepatic stellate cell) cells. Interestingly, exosomes from HBV infected HepG2-NTCP cells upregulated OCT4/miR-1246/β-catenin expression as well as α-SMA, Col1A and TIMP-1 in LX2 cells. These fibrogenic effects were inhibited by HBx gRNA. Moreover, 26 HBV infected patients were enrolled in this study. The expression of miR-1246 and β-catenin in liver tissue were strongly correlated with LF. These results showed that HBV induced LF through exosomal OCT4/miR-1246/β-catenin Pathway, which lay a basis for LF treatment.</p></div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 10\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70521\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70521","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Accumulating research highlights the critical involvement of octamer-binding transcription factor 4 (OCT4) in liver fibrosis (LF) development. However, the mechanistic relationship between OCT4 and hepatitis B virus (HBV)-associated LF remains unclear. HBV exposure markedly upregulated OCT4 and miR-1246 expression in both HepAD38 and HepG2-NTCP cell lines. These effects were reversed by entecavir treatment or the Hepatitis B X (HBx) knockdown. Furthermore, overexpression of OCT4 enhanced expression of miR-1246, β-catenin, and LF-associated genes in LX2 (Hepatic stellate cell) cells. Interestingly, exosomes from HBV infected HepG2-NTCP cells upregulated OCT4/miR-1246/β-catenin expression as well as α-SMA, Col1A and TIMP-1 in LX2 cells. These fibrogenic effects were inhibited by HBx gRNA. Moreover, 26 HBV infected patients were enrolled in this study. The expression of miR-1246 and β-catenin in liver tissue were strongly correlated with LF. These results showed that HBV induced LF through exosomal OCT4/miR-1246/β-catenin Pathway, which lay a basis for LF treatment.
期刊介绍：
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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