title: miR-140-5p regulates adipocyte differentiation by targeting transforming growth factor-β signaling.
abstract: 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.
authors.affiliation: Collaborative Innovation Center of Tianjin Metabolic Diseases Hospital, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital &Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Endocrinology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Chang
authors.affiliation: Collaborative Innovation Center of Tianjin Metabolic Diseases Hospital, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital &Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center of Tianjin Metabolic Diseases Hospital, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital &Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Integrative Medicine, Tianjin Traditional Medical University, Tianjin 300193, China.
authors.forename: Haixiao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Endocrinology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Ma
authors.affiliation: College of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center of Tianjin Metabolic Diseases Hospital, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital &Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D022763:CCAAT-Enhancer-Binding Protein-alpha; C547828:MIRN140 microRNA, mouse; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse