RT Journal Article
T1 Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients
A1 Farup, Jean
A1 Just, Jesper
A1 de Paoli, Frank
A1 Lin, Lin
A1 Jensen, Jonas Brorson
A1 Billeskov, Tine
A1 Sánchez-Román Rojas, Inés
A1 Cömert, Cagla
A1 Møller, Andreas Much
A1 Madaro, Luca
A1 Groppa, Elena
A1 Fred, Rikard Göran
A1 Kampmann, Ulla
A1 Gormsen, Lars
A1 Pedersen, Steen
A1 Bross, Peter
A1 Stevnsner, Tinna
A1 Eldrup, Nikolaj
A1 Pers, Tune
A1 Rossi, Fabio
A1 Puri, Pier Lorenzo
A1 Jessen, Niels
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.
PB Cell Press
SN 1550-4131
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/96773
UL https://hdl.handle.net/20.500.14352/96773
LA eng
NO Farup, Jean, et al. «Human Skeletal Muscle CD90+ Fibro-Adipogenic Progenitors Are Associated with Muscle Degeneration in Type 2 Diabetic Patients». Cell Metabolism, vol. 33, n.o 11, noviembre de 2021, pp. 2201-2214.e10. https://doi.org/10.1016/j.cmet.2021.10.001.
NO Funding was provided by the A.P. Møller Foundation; Riisfort Foundation; Toyota Foundation; Independent Research Fund Denmark (DFF–5053-00195 to J.F.); Steno Diabetes Center Aarhus, which is partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF17OC0027242 to N.J. and NNF16OC0021496 to T.H.P.); Lundbeck Foundation (R190-2014-3904 to T.H.P.); Roche per la Ricerca 2019 to L.M.; and NIH/NIAMS (R01AR076247-01 to P.L.P.).
NO A.P. Møller Foundation
NO Riisfort Foundation
NO Toyota Foundation
NO Independent Research Fund Denmark
NO Novo Nordisk Foundation
NO Lundbeck Foundation
NO National Institutes of Health
DS Docta Complutense
RD 12 abr 2025