title: Peroxisome Proliferator-Activated Receptor Gamma Negatively Regulates the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Toward Myofibroblasts in Liver Fibrogenesis.
abstract: OBJECTIVE
  Bone marrow-derived mesenchymal stem cells (BMSCs) have been confirmed to have capacity to differentiate toward hepatic myofibroblasts, which contribute to fibrogenesis in chronic liver diseases. Peroxisome proliferator-activated receptor gamma (PPARx03B3;), a ligand-activated transcription factor, has gained a great deal of recent attention as it is involved in fibrosis and cell differentiation. However, whether it regulates the differentiation of BMSCs toward myofibroblasts remains to be defined.
  
  
  METHODS
  Carbon tetrachloride or bile duct ligation was used to induce mouse liver fibrosis. Expressions of PPARx03B3;, α-smooth muscle actin, collagen α1 (I) and collagen α1 (III) were detected by real-time RT-PCR and Western blot or immunofluorescence assay.
  
  
  RESULTS
  PPARx03B3; expression was decreased in mouse fibrotic liver. In addition, PPARx03B3; was declined during the differentiation of BMSCs toward myofibroblasts induced by transforming growth factor β1. Activation of PPARx03B3; stimulated by natural or synthetic ligands suppressed the differentiation of BMSCs. Additionally, knock down of PPARx03B3; by siRNA contributed to BMSC differentiation toward myofibroblasts. Furthermore, PPARx03B3; activation by natural ligand significantly inhibited the differentiation of BMSCs toward myofibroblasts in liver fibrogenesis and alleviated liver fibrosis.
  
  
  CONCLUSIONS
  PPARx03B3; negatively regulates the differentiation of BMSCs toward myofibroblasts, which highlights a further mechanism implicated in the BMSC differentiation.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Jia
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Weiyang
authors.initials: W
authors.lastname: Li
authors.forename: Jieshi
authors.initials: J
authors.lastname: Xie
authors.forename: Le
authors.initials: L
authors.lastname: Yang
authors.forename: Liying
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation; D008103:Liver Cirrhosis / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008813:Mice, Inbred ICR; D058628:Myofibroblasts / Q000737:chemistry*; D047495:PPAR gamma / Q000502:physiology*
chemical_list: D047495:PPAR gamma