miR-140-5p regulates adipocyte differentiation by targeting transforming growth factor-β signaling

• Published in: Scientific reports 2015-12, Vol.5 (1), p.18118-18118, Article 18118
• Main Authors: Zhang, Xin, Chang, Ailing, Li, Yongmei, Gao, Yifei, Wang, Haixiao, Ma, Zhongshu, Li, Xiaoxia, Wang, Baoli
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/100; 13/44; 13/89; 3' Untranslated Regions - genetics; 38; 38/109; 3T3-L1 Cells; 631/337/384; 631/532/1360; 631/80/86; Adipocytes - cytology; Adipocytes - metabolism; Animals; CCAAT-Enhancer-Binding Protein-alpha - genetics; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Cell Differentiation - genetics; Cell Line; Cells, Cultured; Gene Expression Regulation; Gene Knockdown Techniques; Humanities and Social Sciences; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; multidisciplinary; Osteoblasts - cytology; Osteoblasts - metabolism; Promoter Regions, Genetic - genetics; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Science; Signal Transduction - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18118

Recent emerging studies of miRNAs in adipocyte commitment provide new insights to understand the molecular basis of adipogenesis. The current study indicated that miR-140-5p was altered in primary cultured marrow stromal cells and established progenitor lines after adipogenic and/or osteogenic treatment. miR-140-5p was increased in adipose tissue in db/db obese mice vs. lean mice. Supplementing miR-140-5p activity induced stromal cell ST2 and preadipocyte 3T3-L1 to differentiate into mature adipocytes. Conversely, inhibition of the endogenous miR-140-5p repressed ST2 and 3T3-L1 to fully differentiate. By contrast, knockdown of the endogenous miR-140-5p enhanced osteoblast differentiation. Transforming growth factor-β receptor I (Tgfbr1) was shown to be a direct target of miR-140-5p. Supplementing miR-140-5p in ST2 reduced the level of TGFBR1 protein, while suppression of endogenous miR-140-5p increased TGFBR1. Overexpression of Tgfbr1 inhibited, whereas knockdown of Tgfbr1 promoted adipogenic differentiation of ST2 cells. Further investigation of mechanisms that control miR-140-5p expression revealed that C/EBPα induced transcriptional activity of the miR-140-5p promoter. Removal of the putative response element of C/EBP from the promoter abolished the enhancement of the promoter activity by C/EBPα, suggesting that C/EBPα transcriptionally controls miR-140-5p expression. Taken together, our study provides evidences that miR-140-5p regulates adipocyte differentiation through a C/EBP/miR-140-5p/TGFBR1 regulatory feedback loop.