Human skeletal muscle CD90+ fibro-adipogenicprogenitors are associated with muscledegeneration in type 2 diabetic patients 作者：Farup J, Just J, de Paoli F, Lin L, Jensen JB, Billeskov T, Roman IS, Cömert C, Møller AB, Madaro L, Groppa E, Fred RG, Kampmann U, Gormsen LC, Pedersen SB, Bross P, Stevnsner T, Eldrup N, Pers TH, Rossi FMV, Puri PL, Jessen N(Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark; Research Laboratory for Biochemical Pathology, Department of Clinical Medicine, Aarhus University, Aarhus 8200, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus 8200, Denmark; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus 8200, Denmark.) 發表情況：Cell Metabolism. 2021 Nov 2;33(11):2201-2214.e11.doi: 10.1016/j.cmet.2021.10.001. Epub 2021 Oct 21. PMID: 34678202.
Type 2 diabetes mellitus (T2DM) is associated with impaired skeletal muscle function and degeneration of the skeletal muscles. However, the mechanisms underlying the degeneration are not well described in human skeletal muscle. Here we show that skeletal muscle of T2DM patients exhibit degenerative remodeling of the extracellular matrix that is 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 it promotes 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 in T2DM patients. These data identify a PDGFdriven conversion of a subpopulation of FAPs as a key event in the fibrosis development in T2DM muscle.
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