NHC Key Lab of Hormones and Development, Tianjin Key Lab of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
FASEB J. 2020 Jul;34(7):9207-9222. doi: 10.1096/fj.201901562RR. Epub 2020 May 29.
MicroRNAs have been reported to play a role in adipogenesis and obesity. This study was performed to investigate the role of miR-196b-5p in adipogenesis and the mechanism involved. The data revealed that miR-196b-5p expression increased in primary or established marrow stromal progenitor cells after adipogenic treatment. Supplementing miR-196b-5p in the progenitor cells stimulated adipogenic differentiation and lipogenesis, along with the induction of adipogenic and lipogenic factors. Conversely, inhibition of endogenous miR-196b-5p blocked adipogenesis and lipogenesis. Tuberous sclerosis 1 (Tsc1) and transforming growth factor-β receptor 1 (TGFBR1) were demonstrated to be the direct target genes of miR-196b-5p. Supplementing miR-196b-5p activity in progenitor cells reduced the protein level of TSC1 and activated mammalian target of rapamycin complex 1 (mTORC1) signaling. We further demonstrated that the perturbation of TSC1 in progenitor cells altered the trend of adipogenic differentiation and lipogenesis. Overexpression of Tsc1 or inactivation of mTORC1 signaling attenuated the stimulation of adipogenic differentiation and lipogenesis by miR-196b-5p. Overexpression of Tgfbr1 also partially blocked the adipogenic effect of miR-196b-5p. Further investigations demonstrated that zinc finger E-box-binding homeobox 1 (ZEB1) transcriptionally upregulated miR-196b-5p expression. The current study suggests that miR-196b-5p promotes adipogenic differentiation and lipogenesis in progenitor cells through targeting TSC1 and TGFBR1 and therefore regulating mTORC1 and TGF-β signaling.
微小 RNA 已被报道在脂肪生成和肥胖中发挥作用。本研究旨在探讨 miR-196b-5p 在脂肪生成中的作用及其涉及的机制。数据显示，在脂肪生成处理后，原代或已建立的骨髓基质祖细胞中的 miR-196b-5p 表达增加。在祖细胞中补充 miR-196b-5p 可刺激脂肪生成和脂肪生成，同时诱导脂肪生成和脂肪生成因子。相反，内源性 miR-196b-5p 的抑制阻断了脂肪生成和脂肪生成。结节性硬化症 1（TSC1）和转化生长因子-β受体 1（TGFBR1）被证明是 miR-196b-5p 的直接靶基因。在祖细胞中补充 miR-196b-5p 活性可降低 TSC1 蛋白水平并激活哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）信号。我们进一步证明，祖细胞中 TSC1 的干扰改变了脂肪生成分化和脂肪生成的趋势。TSC1 在祖细胞中的过表达或 mTORC1 信号的失活减弱了 miR-196b-5p 对脂肪生成分化和脂肪生成的刺激作用。Tgfbr1 的过表达也部分阻断了 miR-196b-5p 的脂肪生成作用。进一步的研究表明，锌指 E 盒结合同源盒 1（ZEB1）转录上调 miR-196b-5p 的表达。本研究表明，miR-196b-5p 通过靶向 TSC1 和 TGFBR1 促进祖细胞中的脂肪生成分化和脂肪生成，从而调节 mTORC1 和 TGF-β 信号。
