SPRY4 promotes adipogenic differentiation of human mesenchymal stem cells through the MEK–ERK1/2 signaling pathway

Obesity is a chronic metabolic disorder characterized by the accumulation of excess fat in the body. Preventing and controlling obesity by inhibiting the adipogenic differentiation of mesenchymal stem cells (MSCs) and thereby avoiding the increase of white adipose tissue is safe and effective. Recent studies have demonstrated that Sprouty proteins (SPRYs) are involved in cell differentiation and related diseases. However, the role and mechanism of SPRY4 in MSC adipogenic differentiation remain to be explored. Here, we found that SPRY4 positively correlates with the adipogenic differentiation of human adipose-derived MSCs (hAMSCs). Via gain- and loss-of-function experiments, we demonstrated that SPRY4 promotes hAMSC adipogenesis both in vitro and in vivo. Mechanistically, SPRY4 functioned by activating the MEK–ERK1/2 pathway. Our findings provide new insights into a critical role for SPRY4 as a regulator of adipogenic differentiation, which may illuminate the underlying mechanisms of obesity and suggest the potential of SPRY4 as a novel treatment option.

肥胖症是一种以体内过量脂肪堆积为特征的慢性代谢紊乱疾病。通过抑制间充质干细胞（mesenchymal stem cells，MSCs）的成脂分化，进而避免白色脂肪组织异常增生，以此预防和控制肥胖是安全且有效的策略。近期研究证实，Spry家族蛋白（Sprouty proteins，SPRYs）参与细胞分化过程及相关疾病的发生发展。然而，SPRY4在MSCs成脂分化中的具体作用与调控机制仍有待探索。本研究发现，SPRY4与人脂肪来源间充质干细胞（human adipose-derived MSCs，hAMSCs）的成脂分化水平呈正相关。通过功能获得与功能缺失实验，我们证实SPRY4在体外与体内均可促进hAMSCs的成脂分化过程。机制层面，SPRY4通过激活MEK-ERK1/2信号通路发挥其调控功能。本研究揭示了SPRY4作为成脂分化调控因子的关键作用，为阐明肥胖的潜在发病机制提供了全新视角，同时提示SPRY4有望成为肥胖治疗的新型潜在靶点。