title: TGF-β/SMAD Pathway and Its Regulation in Hepatic Fibrosis.
abstract: Transforming growth factor-beta1 (TGF-β1), a key member in the TGF-β superfamily, plays a critical role in the development of hepatic fibrosis. Its expression is consistently elevated in affected organs, which correlates with increased extracellular matrix deposition. SMAD proteins have been studied extensively as pivotal intracellular effectors of TGF-β1, acting as transcription factors. In the context of hepatic fibrosis, SMAD3 and SMAD4 are pro-fibrotic, whereas SMAD2 and SMAD7 are protective. Deletion of SMAD3 inhibits type I collagen expression and blocks epithelial-myofibroblast transition. In contrast, disruption of SMAD2 upregulates type I collagen expression. SMAD4 plays an essential role in fibrosis disease by enhancing SMAD3 responsive promoter activity, whereas SMAD7 negatively mediates SMAD3-induced fibrogenesis. Accumulating evidence suggests that divergent miRNAs participate in the liver fibrotic process, which partially regulates members of the TGF-β/SMAD signaling pathway. In this review, we focus on the TGF-β/SMAD and other relative signaling pathways, and discussed the role and molecular mechanisms of TGF-β/SMAD in the pathogenesis of hepatic fibrosis. Moreover, we address the possibility of novel therapeutic approaches to hepatic fibrosis by targeting to TGF-β/SMAD signaling.
authors.affiliation: School of Pharmacy (FX, DZ, LZ)|Anhui Medical University, Hefei 230022, ChinaInstitute for Liver Diseases (FX, DZ, LZ),
authors.forename: Fengyun
authors.initials: F
authors.lastname: Xu
authors.affiliation: Anhui Medical University, Hefei 230022, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical University (CL)
authors.forename: Changwei
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Pharmacy (FX, DZ, LZ)|Anhui Medical University, Hefei 230022, ChinaInstitute for Liver Diseases (FX, DZ, LZ),
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: School of Pharmacy (FX, DZ, LZ)|Anhui Medical University, Hefei 230022, ChinaInstitute for Liver Diseases (FX, DZ, LZ),
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta
keywords: Epithelial-myofibroblast transition; TGF-β/SMAD; hepatic fibrosis; miRNAs