Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients
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Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients. / Farup, Jean; Just, Jesper; de Paoli, Frank; Lin, Lin; Jensen, Jonas Brorson; Billeskov, Tine; Roman, Ines Sanchez; Cömert, Cagla; Møller, Andreas Buch; Madaro, Luca; Groppa, Elena; Fred, Rikard Göran; Kampmann, Ulla; Gormsen, Lars C.; Pedersen, Steen B.; Bross, Peter; Stevnsner, Tinna; Eldrup, Nikolaj; Pers, Tune H.; Rossi, Fabio M.V.; Puri, Pier Lorenzo; Jessen, Niels.
In: Cell Metabolism, Vol. 33, No. 11, 2021, p. 2201-2214.e11.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients
AU - Farup, Jean
AU - Just, Jesper
AU - de Paoli, Frank
AU - Lin, Lin
AU - Jensen, Jonas Brorson
AU - Billeskov, Tine
AU - Roman, Ines Sanchez
AU - Cömert, Cagla
AU - Møller, Andreas Buch
AU - Madaro, Luca
AU - Groppa, Elena
AU - Fred, Rikard Göran
AU - Kampmann, Ulla
AU - Gormsen, Lars C.
AU - Pedersen, Steen B.
AU - Bross, Peter
AU - Stevnsner, Tinna
AU - Eldrup, Nikolaj
AU - Pers, Tune H.
AU - Rossi, Fabio M.V.
AU - Puri, Pier Lorenzo
AU - Jessen, Niels
N1 - Publisher Copyright: © 2021 Elsevier Inc.
PY - 2021
Y1 - 2021
N2 - 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 PDGF-driven conversion of a subpopulation of FAPs as a key event in the fibrosis development in T2DM muscle.
AB - 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 PDGF-driven conversion of a subpopulation of FAPs as a key event in the fibrosis development in T2DM muscle.
KW - adipocytes
KW - extracellular matrix
KW - fatty degeneration
KW - fibro-adipogenic progenitors
KW - fibroblast
KW - fibrosis
KW - mesenchymal stem cells
KW - skeletal muscle
KW - type 2 diabetes
U2 - 10.1016/j.cmet.2021.10.001
DO - 10.1016/j.cmet.2021.10.001
M3 - Journal article
C2 - 34678202
AN - SCOPUS:85118157720
VL - 33
SP - 2201-2214.e11
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 11
ER -
ID: 284702228