Yan Yi, Yuan Jiahui, Luo Xiaomao, Yu Xiuju, Lu Jiayin, Hou Wei, He Xiaoyan, Zhang Liping, Cao Jing, Wang Haidong
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
Department of Medicine, Nephrology Division, Baylor College of Medicine, Houston, GA, United States.
Front Mol Biosci. 2022 Jun 27;9:907148. doi: 10.3389/fmolb.2022.907148. eCollection 2022.
In recent years, the studies of the role of microRNAs in adipogenesis and adipocyte development and the corresponding molecular mechanisms have received great attention. In this work, we investigated the function of miR-140 in the process of adipogenesis and the molecular pathways involved, and we found that adipogenic treatment promoted the miR-140-5p RNA level in preadipocytes. Over-expression of miR-140-5p in preadipocytes accelerated lipogenesis along with adipogenic differentiation by transcriptional modulation of adipogenesis-linked genes. Meanwhile, silencing endogenous miR-140-5p dampened adipogenesis. Platelet-derived growth factor receptor alpha (PDGFRα) was shown to be a miR-140-5p target gene. miR-140-5p over-expression in preadipocyte 3T3-L1 diminished PDGFRα expression, but silencing of miR-140-5p augmented it. In addition, over-expression of PDGFRα suppressed adipogenic differentiation and lipogenesis, while its knockdown enhanced these biological processes of preadipocyte 3T3-L1. Altogether, our current findings reveal that miR-140-5p induces lipogenesis and adipogenic differentiation in 3T3-L1 cells by targeting PDGFRα, therefore regulating adipogenesis. Our research provides molecular targets and a theoretical basis for the treatment of obesity-related metabolic diseases.
近年来，关于微小RNA在脂肪生成和脂肪细胞发育中的作用及其相应分子机制的研究受到了广泛关注。在本研究中，我们探究了miR-140在脂肪生成过程中的功能及其涉及的分子途径，发现脂肪生成处理可促进前脂肪细胞中miR-140-5p的RNA水平。在前脂肪细胞中过表达miR-140-5p可通过对脂肪生成相关基因的转录调控加速脂肪生成以及脂肪形成分化。同时，沉默内源性miR-140-5p可抑制脂肪生成。血小板衍生生长因子受体α（PDGFRα）被证明是miR-140-5p的靶基因。在前脂肪细胞3T3-L1中过表达miR-140-5p可降低PDGFRα的表达，但沉默miR-140-5p则可增强其表达。此外，过表达PDGFRα可抑制脂肪形成分化和脂肪生成，而敲低PDGFRα则可增强前脂肪细胞3T3-L1的这些生物学过程。总之，我们目前的研究结果表明，miR-140-5p通过靶向PDGFRα诱导3T3-L1细胞中的脂肪生成和脂肪形成分化，从而调节脂肪生成。我们的研究为肥胖相关代谢疾病的治疗提供了分子靶点和理论基础。
