Peroxisome proliferator-activated receptors gama ameliorates liver fibrosis in non-alcoholic fatty liver disease by inhibiting TGF-β/Smad signaling activation
Qingwei Zhang1
Wenjie Zhao1
Zeqi Sun1
Xinxin Dong1
Liwei Zhu1
Zhen Zhang1
Ximing Chen1
Yingying Hu1
Menghan Du1
Jiamin Li2
Yong Zhang3
1.Department of Pharmacology,College of Pharmacy,and Department of Cardiology,the Second Affiliated Hospital,Harbin Medical University,Harbin 150081,China;Department of Pharmacology,College of Pharmacy,Harbin Medical University,Harbin 150081,China;The State Key Laboratory of Frigid Zone Cardiovascular Diseases(SKLFZCD),and the Key Laboratory of Cardiovascular Medicine Research,Ministry of Education,Harbin 150081,China2.Department of Pharmacology,College of Pharmacy,Harbin Medical University,Harbin 150081,China;The State Key Laboratory of Frigid Zone Cardiovascular Diseases(SKLFZCD),and the Key Laboratory of Cardiovascular Medicine Research,Ministry of Education,Harbin 150081,China;Research Unit of Noninfectious Chronic Diseases in Frigid Zone,Chinese Academy of Medical Sciences,2019RU070,Harbin 150081,China3.Department of Pharmacology,College of Pharmacy,and Department of Cardiology,the Second Affiliated Hospital,Harbin Medical University,Harbin 150081,China;The State Key Laboratory of Frigid Zone Cardiovascular Diseases(SKLFZCD),and the Key Laboratory of Cardiovascular Medicine Research,Ministry of Education,Harbin 150081,China;Research Unit of Noninfectious Chronic Diseases in Frigid Zone,Chinese Academy of Medical Sciences,2019RU070,Harbin 150081,China
摘要：Background:Nonalcoholic fatty liver disease(NAFLD)is a chronic condition characterized by a progressive decline in liver function,leading to disruptions in liver integrity and metabolic function,resulting in lipid deposition and excessive accumulation of extracellular matrix(ECM).The pathogenesis of NAFLD is complex and not yet fully understood,contributing to the absence of specific therapeutic strategies.Peroxisome proliferator-activated receptor gamma(PPARγ)is a ligand-activated transcription factor pivotal in regulating lipid and glucose metabolism.However,the impacts of PPARγ on NAFLD remains insufficiently explored.Thus,this study aimed to investigate the role of PPARγ in NAFLD and its underlying molecular mechanisms.Methods:Chemical detection kits were utilized to quantify collagen content,alanine aminotransferase(ALT),and aspartate aminotransferase(AST)level variations.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess alterations in extracellular matrix-related genes and inflammatory response genes in liver tissue and HepG2 cells,while western blotting was conducted to analyze the levels of both PPARγ and the TGF-β/Smad signaling pathway.Results:Our findings unveiled significantly reduced PPARγ expression in a rat model of NAFLD,leading to subsequent activation of the TGF-β/Smad signaling pathway.Furthermore,PPARγ activation effectively mitigated NAFLD progression by inhibiting inflammation and fibrosis-related gene expression and collagen production.On a cellular level,PPARγ activation was found to inhibit the expression of extracellular matrix-related genes such as matrix metalloproteinase 2(MMP2)and matrix metalloproteinase 9(MMP9),along with inflammatory response genes interleukin(IL)-1β and IL-6.Additionally,PPARγ activation led to a significant decrease in the levels of ALT and AST.At the molecular level,PPARγ notably down-regulated the TGF-β/Smad signaling pathway,which is known to promote liver fibrosis.Conclusion:These groundbreaking findings underscore PPARγ activation as a promising therapeutic approach to delay NAFLD progression by targeting the TGF-β/Smad signaling pathway in hepatic cells.This highlights the potential of PPARγ as a promising therapeutic target for NAFLD management in clinical settings.
机标关键词：fibrosissmadgamaactivatedactivationamelioratesdiseasefatty
论文发表日期：2024-01-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 12-22,中插2 )
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