RGD Reference Report - Peroxisome Proliferator-Activated Receptor Gamma Negatively Regulates the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Toward Myofibroblasts in Liver Fibrogenesis. - Rat Genome Database

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Peroxisome Proliferator-Activated Receptor Gamma Negatively Regulates the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Toward Myofibroblasts in Liver Fibrogenesis.

Authors: Jia, S  Liu, X  Li, W  Xie, J  Yang, L  Li, L 
Citation: Jia S, etal., Cell Physiol Biochem. 2015;37(6):2085-100. doi: 10.1159/000438567. Epub 2015 Nov 25.
RGD ID: 11554658
Pubmed: PMID:26599535   (View Abstract at PubMed)
DOI: DOI:10.1159/000438567   (Journal Full-text)

BACKGROUND/AIMS: 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;, alpha-smooth muscle actin, collagen alpha1 (I) and collagen alpha1 (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 beta1. 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPARGHumanChemical and Drug Induced Liver Injury  ISOPparg (Mus musculus)mRNA and protein:decreased expression:liverRGD 
PpargRatChemical and Drug Induced Liver Injury  ISOPparg (Mus musculus)mRNA and protein:decreased expression:liverRGD 
PpargMouseChemical and Drug Induced Liver Injury  IEP mRNA and protein:decreased expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pparg  (peroxisome proliferator-activated receptor gamma)

Genes (Mus musculus)
Pparg  (peroxisome proliferator activated receptor gamma)

Genes (Homo sapiens)
PPARG  (peroxisome proliferator activated receptor gamma)


Additional Information