Chen Lin, Chen Yuanwei, Zhang Sheng, Ye Lanfeng, Cui Junhui, Sun Quan, Li Kaide, Wu Hanjiang, Liu Lei
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China; Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, P. R. China.
J Cell Biochem. 2015 Jun;116(6):969-76. doi: 10.1002/jcb.25050.
A better understanding of the molecular mechanisms in adipogenesis may provide new insights into adipose tissue-related diseases. Recently, microRNAs (miRNAs) have emerged as a class of epigenetic regulators of stem cell differentiation. In this study, we found that miR-540 was an essential negative regulator of adipogenic differentiation in adipose tissue-derived stromal cells (ADSCs). Lentivirus-mediated overexpression of miR-540 resulted in blockade of the expression of C/EBP-α and PPARγ, the two master transcription factors of adipogenesis, and deficient lipid accumulation, whereas inhibition of miR-540 promoted these processes. Target gene reporter assays showed that miR-540 directly targeted the 3'-untranslated region (3'UTR) of PPARγ, resulting in a decrease of PPARγ protein expression. Collectively, these data suggest that miR-540 represents a new adipogenic inhibitor by, at least in part, targeting PPARγ.
对脂肪生成分子机制的深入理解可能为与脂肪组织相关的疾病提供新的见解。最近，微小RNA（miRNA）已成为一类干细胞分化的表观遗传调节因子。在本研究中，我们发现miR-540是脂肪组织来源的基质细胞（ADSC）中脂肪生成分化的重要负调节因子。慢病毒介导的miR-540过表达导致脂肪生成的两个主要转录因子C/EBP-α和PPARγ的表达受阻，以及脂质积累不足，而抑制miR-540则促进了这些过程。靶基因报告分析表明，miR-540直接靶向PPARγ的3'-非翻译区（3'UTR），导致PPARγ蛋白表达下降。总体而言，这些数据表明miR-540至少部分通过靶向PPARγ代表一种新的脂肪生成抑制剂。
