Peroxisome proliferator-activated receptor gamma/signal transducers and activators of transcription 5A pathway plays a key factor in adipogenesis of human bone marrow-derived stromal cells and 3T3-L1 preadipocytes

Abstract

Adipogenesis is largely dependent on the signal transducers and activators of transcription (STAT) pathway. However, the molecular mechanism of the STAT pathway in the adipogenesis of human bone marrow-derived stromal cells (hBMSCs) remains not well understood. The purpose of this research was to characterize the transcriptional regulation involved in expression of STAT5A and STAT5B during adipogenesis in hBMSCs and 3T3-L1 cells. The expression of STAT5A and STAT5B increases with the onset of adipogenesis in hBMSCs and 3T3-L1 cells. The PPAR response elements regulatory element of STAT5A exists at a promoter region ranging from -346 to -101, and the CCAAT/enhancer-binding protein (C/EBP) regulatory element is located at -196 to -118 of the STAT5B promoter. C/EBPβ and C/EBPα bound to the STAT5B promoter region, whereas peroxisome proliferator-activated receptor γ (PPARγ) bound to STAT5A. RNA interference of STAT5A completely blocked differentiation, whereas the inhibition of STAT5B only partially blocked differentiation. We propose that C/EBPα, C/EBPβ, and PPARγ control adipogenesis by regulating STAT5B and STAT5A and that STAT5A is necessary, whereas STAT5B plays a supplementary role during adipogenesis. Further, the regulation of PPARγ-STAT5 by C/EBPβ signaling seems to be the crucial adipogenesis pathway-initiating cascade of the various adipogenic genes.