丹麦奥尔胡斯大学Niels Jessen和Jean Farup研究组合作发现人骨骼肌CD90+纤维脂肪祖细胞 (FAP)与2 型糖尿病(T2DM)患者肌肉退化相关。相关论文于2021年10月21日发表在《细胞—代谢》杂志上。

他们显示 T2DM 患者的骨骼肌表现出细胞外基质的退行性重塑，这与以THY1 (CD90)的表达为标志的FAP亚群-（FAPCD90+）的选择性增加有关。他们将血小板衍生生长因子 (PDGF) 确定为关键的 FAP 调节剂，因为它以脂肪生成为代价促进增殖和胶原蛋白生成。FAPsCD90+ 显示 PDGF 模拟表型，具有高增殖活性、克隆形成性和细胞外基质的产生。用二甲双胍进行体外处理后，FAPCD90+ 增殖减少。此外，二甲双胍治疗降低了 T2DM 患者的 FAP 含量。这些数据将 PDGF 驱动的 FAP 亚群转化确定为 T2DM 肌肉纤维化发展的关键事件。

据了解，T2DM与骨骼肌功能受损和骨骼肌退化有关。然而，在人类骨骼肌中并没有很好地描述退化的潜在机制。

附：英文原文

Title: Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients

Author: Jean Farup, Jesper Just, Frank de Paoli, Lin Lin, Jonas Brorson Jensen, Tine Billeskov, Ines Sanchez Roman, Cagla Cmert, Andreas Buch Mller, Luca Madaro, Elena Groppa, Rikard Gran Fred, Ulla Kampmann, Lars C. Gormsen, Steen B. Pedersen, Peter Bross, Tinna Stevnsner, Nikolaj Eldrup, Tune H. Pers, Fabio M.V. Rossi, Pier Lorenzo Puri, Niels Jessen

Issue&Volume: 2021-10-21

Abstract: Type 2 diabetes mellitus (T2DM) is associated with impaired skeletal muscle functionand degeneration of the skeletal muscles. However, the mechanisms underlying the degenerationare not well described in human skeletal muscle. Here we show that skeletal muscleof T2DM patients exhibit degenerative remodeling of the extracellular matrix thatis associated with a selective increase of a subpopulation of fibro-adipogenic progenitors(FAPs) marked by expression of THY1 (CD90)—the FAPCD90+. We identify platelet-derived growth factor (PDGF) as a key FAP regulator, as itpromotes proliferation and collagen production at the expense of adipogenesis. FAPsCD90+ display a PDGF-mimetic phenotype, with high proliferative activity, clonogenicity,and production of extracellular matrix. FAPCD90+ proliferation was reduced by in vitro treatment with metformin. Furthermore, metformin treatment reduced FAP content inT2DM patients. These data identify a PDGF-driven conversion of a subpopulation ofFAPs as a key event in the fibrosis development in T2DM muscle.

DOI: 10.1016/j.cmet.2021.10.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00479-4