Title: Smad1/5/8 are myogenic regulators of murine and human mesoangioblasts
Authors: Costamagna, Domiziana ×
Quattrocelli, Mattia
van Tienen, F
Umans, Lieve
de Coo, If
Zwijsen, An
Huylebroeck, Danny
Sampaolesi, Maurilio #
Issue Date: Oct-2015
Series Title: Journal of Molecular Cell Biology vol:8 issue:1 pages:73-87
Article number: mjv059
Abstract: Mesoangioblasts (MABs) are vessel-associated stem cells that express pericyte marker genes and participate in skeletal muscle regeneration. Molecular circuits that regulate the myogenic commitment of MABs are still poorly characterized. The critical role of bone morphogenetic protein (BMP) signalling during proliferation and differentiation of adult myogenic precursors, such as satellite cells, has recently been established. We evaluated whether BMP signalling impacts on the myogenic potential of embryonic and adult MABs both in vitro and in vivo. Addition of BMP inhibited MAB myogenic differentiation, whereas interference with the interactions between BMPs and receptor complexes induced differentiation. Similarly, siRNA-mediated knockdown of Smad8 in Smad1/5-null MABs or inhibition of SMAD1/5/8 phosphorylation with Dorsomorphin (DM) also improved myogenic differentiation, demonstrating a novel role of SMAD8. Moreover, using a transgenic mouse model of Smad8 deletion, we demonstrated that the absence of SMAD8 protein improved MAB myogenic differentiation. Furthermore, once injected into α-Sarcoglycan (Sgca)-null muscles, DM-treated MABs were more efficacious to restore α-sarcoglycan (αSG) protein levels and re-establish functional muscle properties. Similarly, in acute muscle damage, DM-treated MABs displayed a better myogenic potential compared with BMP-treated and untreated cells. Finally, SMADs also control the myogenic commitment of human MABs (hMABs). BMP signalling antagonists are therefore novel candidates to improve the therapeutic effects of hMABs.
ISSN: 1674-2788
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Embryo and Stemcells (-)
Stem Cell Biology and Embryology (+)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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