期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 18, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ijms18040842
关键词
human bone marrow mesenchymal stem cell; adipogenesis; retinoid; retinoic acid receptor beta (RAR beta); TGF beta/SMAD pathway; Wnt/beta-catenin pathway
资金
- National Natural Science Foundation of China [81260283]
Retinoids may regulate cell differentiation as ligands of retinoic acid receptors (RARs) and/or retinoid X receptors (RXRs). We showed that RAR agonists promoted adipogenesis by upregulating the expression of CCAAT/enhancer-binding protein beta (C/EBP beta) in the early stages, but blocked adipogenesis at a later stage in human bone marrow mesenchymal stem cells (hBMSCs). RXR agonists promoted adipogenesis at all time points in hBMSCs. The effect of RAR agonists was mediated mainly by the RAR beta subtype. RAR agonists, in contrast to RXR agonists, significantly promoted the expression of RAR beta. Knockdown of the RAR beta gene via small hairpin RNA (shRNA) attenuated the inhibition of RAR agonists toward adipogenesis. Furthermore, we found that RAR agonists upregulated the transforming growth factor beta (TGF beta)/SMAD pathway and Wnt/beta-catenin pathway on adipogenesis in hBMSCs, and the stimulating effects were noticeably decreased with the RAR beta gene knockdown. Both RAR agonists and RXR agonists inhibited adipogenesis and blocked the promoter activity of C/EBP beta and peroxisome proliferator-activated receptor gamma (PPAR gamma) in SW872 cell. These results indicated the RAR agonists perform dual roles in adipogenesis in hBMSCs, and the TGF beta /SMAD pathway and Wnt/beta-catenin pathway may involve the inhibitory effect of RAR agonists. RAR beta is the main receptor subtype mediating the effect. The roles of RXR agonists in adipogenesis exhibited cell type-specific differences, and may be based on the integration of signals from different RXR dimers.
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