He Ting, Wang Shuai, Li Shengnan, Shen Huanming, Hou Lingfeng, Liu Yunjia, Wei Yixin, Xie Fuan, Zhang Zhiming, Zhao Zehang, Mo Chunli, Guo Huiling, Huang Qingsong, Zhang Rui, Shen Dongyan, Li Boan
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China.
School of Medicine, Henan Polytechnic University, Jiaozuo, Henan 454000, China.
iScience. 2023 Feb 28;26(4):106289. doi: 10.1016/j.isci.2023.106289. eCollection 2023 Apr 21.
Preadipocyte determination expanding the pool of preadipocytes is a vital process in adipocyte hyperplasia, but the molecular mechanisms underlying this process are yet to be elucidated. Herein, SRY-related HMG box transcription factor 4 (SOX4) was identified as a critical target in response to BMP4- and TGFβ-regulated preadipocyte determination. SOX4 deficiency is sufficient to promote preadipocyte determination in mesenchymal stem cells (MSCs) and acquisition of preadipocyte properties in nonadipogenic lineages, while its overexpression impairs the adipogenic capacity of preadipocytes and converts them into nonadipogenic lineages. Mechanism studies indicated that SOX4 activates and cooperates with LEF1 to retain the nuclear localization of β-catenin, thus mediating the crosstalk between TGFβ/BMP4 signaling pathway and Wnt signaling pathway to regulate the preadipocyte determination. studies demonstrated that SOX4 promotes the adipogenic-nonadipogenic conversion and suppresses the adipocyte hyperplasia. Together, our findings highlight the importance of SOX4 in regulating the adipocyte hyperplasia in obesity.
前脂肪细胞的确定（即扩大前脂肪细胞池）是脂肪细胞增生中的一个重要过程，但其潜在的分子机制尚待阐明。在此，SRY相关的HMG盒转录因子4（SOX4）被确定为响应BMP4和TGFβ调节的前脂肪细胞确定的关键靶点。SOX4缺陷足以促进间充质干细胞（MSC）中的前脂肪细胞确定，并使非脂肪生成谱系获得前脂肪细胞特性，而其过表达则损害前脂肪细胞的成脂能力并将它们转化为非脂肪生成谱系。机制研究表明，SOX4激活LEF1并与之协同作用，以保持β-连环蛋白的核定位，从而介导TGFβ/BMP4信号通路与Wnt信号通路之间的串扰，以调节前脂肪细胞的确定。研究表明，SOX4促进成脂-非成脂转化并抑制脂肪细胞增生。总之，我们的研究结果突出了SOX4在调节肥胖中脂肪细胞增生方面的重要性。
