State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Cell Prolif. 2019 Jul;52(4):e12631. doi: 10.1111/cpr.12631. Epub 2019 Apr 30.
Growth differentiation factor 11 (GDF11), an emerging secreted member of the TGF-beta superfamily, plays essential roles in development, physiology and multiple diseases; however, its role during adipogenic differentiation and the underlying mechanisms remains poorly understood.
Bone marrow-derived human mesenchymal stem cells (hMSCs) and 3T3-L1 pre-adipocytes were induced with adipogenic culture medium supplementing with different concentrations of recombinant GDF11 (rGDF11 0, 10, 50, 100 ng mL ). Oil Red O staining, qRT-PCR analysis, Western blot analysis and immunofluorescence staining were performed to assay adipogenesis.
For both hMSCs and 3T3-L1 pre-adipocytes, the presence of rGDF11 leads to a dose-dependent reduction of intracellular lipid droplet accumulation and suppressed adipogenic-related gene expression. Mechanically, GDF11 inhibits adipogenesis by activating Smad2/3-dependent TGF-beta signalling pathway, and these inhibitory effects could be restored by SB-431542, a pharmacological TGF-beta type I receptor inhibitor.
Taken together, our data indicates that GDF11 inhibits adipogenic differentiation in both hMSCs and 3T3-L1 pre-adipocytes by activating Smad2/3-dependent TGF-beta signalling pathway.
生长分化因子 11（GDF11）是转化生长因子-β超家族中的一种新兴分泌成员，在发育、生理和多种疾病中发挥重要作用；然而，其在脂肪生成分化中的作用及其潜在机制仍知之甚少。
用含有不同浓度重组 GDF11（rGDF110、10、50、100ng/ml）的脂肪生成培养基诱导骨髓来源的人间充质干细胞（hMSCs）和 3T3-L1 前脂肪细胞。进行油红 O 染色、qRT-PCR 分析、Western blot 分析和免疫荧光染色，以检测脂肪生成。
对于 hMSCs 和 3T3-L1 前脂肪细胞，rGDF11 的存在导致细胞内脂滴积累呈剂量依赖性减少，并抑制脂肪生成相关基因的表达。在机制上，GDF11 通过激活 Smad2/3 依赖性 TGF-β信号通路抑制脂肪生成，这些抑制作用可被 SB-431542 恢复，SB-431542 是一种药理学 TGF-β Ⅰ型受体抑制剂。
总之，我们的数据表明，GDF11 通过激活 Smad2/3 依赖性 TGF-β信号通路抑制 hMSCs 和 3T3-L1 前脂肪细胞的脂肪生成分化。
