生长分化因子11通过激活素受体样激酶5/ Kruppel样因子15/β-连环蛋白/过氧化物酶体增殖物激活受体γ级联反应抑制人脂肪来源间充质干细胞的脂肪生成。
GDF11 inhibits adipogenesis of human adipose-derived stromal cells through ALK5/KLF15/β-catenin/PPARγ cascade.
作者信息
Lin Shimin, Zhong Lishan, Chen Jingyi, Zhao Zibo, Wang Rongze, Zhu Yexuan, Liu Junwei, Wu Yanting, Ye Cuifang, Jin Fujun, Ren Zhe
机构信息
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China.
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China.
出版信息
Heliyon. 2023 Jan 21;9(2):e13088. doi: 10.1016/j.heliyon.2023.e13088. eCollection 2023 Feb.
Obesity is a metabolic disease characterized by excessive fat storage, and the adipogenic differentiation of adipose-derived stromal cells (ADSCs) is closely linked to its occurrence. Growth differentiation factor 11 (GDF11), a well-known molecule in the field of anti-aging, also has great potential in regulating stem cell differentiation. In this study, we found that GDF11 inhibited adipogenic differentiation of human ADSCs in vitro by activating the WNT/β-catenin and SMAD2/3 pathways while inhibiting the AKT pathway. Moreover, the transcription factor Kruppel-like factor 15 (KLF15) was discovered to be an important downstream factor for GDF11 in inhibiting adipogenesis via the WNT/β-catenin pathway. Furthermore, AlphaFold2 structure prediction and inhibitor-blocking experiments revealed that ALK5 is a functional receptor of GDF11. Collectively, we demonstrated that GDF11 is a potential target for inhibiting adipogenic differentiation and combating obesity.
肥胖是一种以脂肪过度储存为特征的代谢性疾病，脂肪来源的基质细胞（ADSCs）的成脂分化与其发生密切相关。生长分化因子11（GDF11）是抗衰老领域的一个知名分子，在调节干细胞分化方面也具有巨大潜力。在本研究中，我们发现GDF11通过激活WNT/β-连环蛋白和SMAD2/3途径，同时抑制AKT途径，在体外抑制人ADSCs的成脂分化。此外，转录因子Kruppel样因子15（KLF15）被发现是GDF11通过WNT/β-连环蛋白途径抑制脂肪生成的重要下游因子。此外，AlphaFold2结构预测和抑制剂阻断实验表明，ALK5是GDF11的功能受体。我们共同证明，GDF11是抑制成脂分化和对抗肥胖的潜在靶点。
Zotero 插件