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.

蛋白质精氨酸甲基转移酶（Protein arginine methyltransferases, PRMTs）在多种细胞生物学过程中发挥关键调控作用。在PRMT家族成员中，蛋白质精氨酸甲基转移酶7（Protein arginine methyltransferase 7, PRMT7）可催化ω-单甲基精氨酸的生成。已有研究证实，人类PRMT7缺陷会引发严重的发育异常；而小鼠体内PRMT7敲低则会导致免疫细胞与肌肉干细胞功能缺陷。本研究阐明了PRMT7在调控脂肪生成中的作用：实验结果显示，在间充质干细胞（mesenchymal stem cells, MSCs）的成脂分化过程中，PRMT7的表达水平会受到抑制。PRMT7敲低可显著增强成脂分化能力，而过表达PRMT7的细胞其成脂分化能力则显著下降。机制层面研究发现，PRMT7敲低能够激活胰岛素样生长因子-1（insulin-like growth factors-1, IGF1）的表达，进而证实PRMT7通过IGF1信号通路调控成脂分化。本研究最终证明，PRMT7是治疗代谢性疾病的重要分子靶点。