PRMT7 regulates adipogenic differentiation of hBMSCs by modulating IGF1 signaling

PRMTs (Protein arginine methyltransferases) play a critical role in several cellular biological processes. Among the PRMT family members, PRMT7(Protein arginine methyltransferase 7) acts as a catalyst for the formation of ω-monomethyl arginine. PRMT7 deficiency in humans has been shown to be associated with significant developmental defects, while PRMT7 knockdown in mice leads to defects in immune cells and muscle stem cells. In the present work, we demonstrate the role of PRMT7 in modulating adipogenesis. Our study showed that PRMT7 expression was impaired during the adipogenesis of MSCs (mesenchymal stem cells). The knockdown of PRMT7 significantly enhanced the adipogenic differentiation, and PRMT7-overexpressing cells displayed decreased capability for adipogenic differentiation. Mechanically, we found that PRMT7 knockdown could activate the expression of IGF1(insulin-like growth factors-1) , and determined that PRMT7 regulates adipogenic differentiation through IGF1 signaling. Our current work demonstrated that PRMT7 is an important molecular target for the treatment of metabolic diseases.蛋白精氨酸甲基转移酶（Protein arginine methyltransferases，PRMTs）在诸多细胞生物学过程中发挥关键作用。在PRMT家族成员中，蛋白精氨酸甲基转移酶7（Protein arginine methyltransferase 7，PRMT7）可催化ω-单甲基精氨酸的生成。研究表明，人类体内PRMT7缺失与严重的发育缺陷密切相关，而小鼠体内PRMT7敲低则会导致免疫细胞与肌肉干细胞出现功能异常。本研究阐明了PRMT7在调控脂肪生成过程中的作用。研究发现，在间充质干细胞（mesenchymal stem cells，MSCs）的脂肪生成过程中，PRMT7的表达会受到抑制。敲低PRMT7可显著增强脂肪分化能力，而过表达PRMT7的细胞则表现出脂肪分化能力的下降。从机制层面而言，我们发现敲低PRMT7可激活胰岛素样生长因子-1（insulin-like growth factors-1，IGF1）的表达，并证实PRMT7通过IGF1信号通路调控脂肪分化。本研究证实PRMT7是治疗代谢性疾病的重要分子靶点。