title: Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3.
abstract: PDZRN3, a member of the PDZRN (or LNX) family of proteins, is essential for the differentiation of mesenchymal stem cells into myotubes, but it plays an inhibitory role in the differentiation of these cells into osteoblasts. Given that mesenchymal stem cells also differentiate into adipocytes, we examined the possible role of PDZRN3 in adipogenesis in mouse 3T3-L1 preadipocytes. The expression of PDZRN3 decreased at both the mRNA and protein levels during adipogenic differentiation. RNAi-mediated depletion of PDZRN3 enhanced the differentiation of 3T3-L1 cells into adipocytes as assessed on the basis of lipid accumulation. The upregulation of aP2 and CCAAT/enhancer-binding protein (C/EBP)-β during adipocyte differentiation was also enhanced in the PDZRN3-depleted cells, as was the induction of peroxisome proliferator-activated receptor-γ (PPARγ), an upstream regulator of aP2 and C/EBPα, at both the mRNA and protein levels. Among transcription factors that control the expression of PPARγ, we found that STAT5b, but not STAT5a, was upregulated in PDZRN3-depleted cells at both mRNA and protein levels. Tyrosine phosphorylation of STAT5b, but not that of STAT5a, was also enhanced at an early stage of differentiation by PDZRN3 depletion. In addition, the expression of C/EBPβ during the induction of differentiation was enhanced at the mRNA and protein levels in PDZRN3-depleted cells. Our results thus suggest that PDZRN3 negatively regulates adipogenesis in 3T3-L1 cells through downregulation of STAT5b and C/EBPβ and consequent suppression of PPARγ expression.
authors.affiliation: Department of Pharmacology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Honda
authors.forename: Aiko
authors.initials: A
authors.lastname: Ishii
authors.forename: Makoto
authors.initials: M
authors.lastname: Inui
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D002352:Carrier Proteins; D047495:PPAR gamma; D050799:STAT5 Transcription Factor; C582444:PDZRN3 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: C/EBPβ; PDZRN3; PPARγ; STAT5; adipogenesis; differentiation