Skip to Main content Skip to Navigation
Journal articles

Gli3 Regulation of Myogenesis Is Necessary for Ischemia-Induced Angiogenesis

Abstract : RATIONALE: A better understanding of the mechanism underlying skeletal muscle repair is required to develop therapies that promote tissue regeneration in adults. Hedgehog signaling has been shown previously to be involved in myogenesis and angiogenesis: 2 crucial processes for muscle development and regeneration. OBJECTIVE: The objective of this study was to identify the role of the hedgehog transcription factor Gli3 in the cross-talk between angiogenesis and myogenesis in adults. METHODS AND RESULTS: Using conditional knockout mice, we found that Gli3 deficiency in endothelial cells did not affect ischemic muscle repair, whereas in myocytes, Gli3 deficiency resulted in severely delayed ischemia-induced myogenesis. Moreover, angiogenesis was also significantly impaired in HSA-Cre(ERT2); Gli3(Flox/Flox) mice, demonstrating that impaired myogenesis indirectly affects ischemia-induced angiogenesis. The role of Gli3 in myocytes was then further investigated. We found that Gli3 promotes myoblast differentiation through myogenic factor 5 regulation. In addition, we found that Gli3 regulates several proangiogenic factors, including thymidine phosphorylase and angiopoietin-1 both in vitro and in vivo, which indirectly promote endothelial cell proliferation and arteriole formation. In addition, we found that Gli3 is upregulated in proliferating myoblasts by the cell cycle-associated transcription factor E2F1. CONCLUSIONS: This study shows for the first time that Gli3-regulated postnatal myogenesis is necessary for muscle repair-associated angiogenesis. Most importantly, it implies that myogenesis drives angiogenesis in the setting of skeletal muscle repair and identifies Gli3 as a potential target for regenerative medicine.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-01777743
Contributor : Laure Penigaud <>
Submitted on : Wednesday, April 25, 2018 - 9:45:54 AM
Last modification on : Wednesday, May 16, 2018 - 11:23:07 AM

Links full text

Identifiers

Citation

Marie-Ange Renault, Soizic Vandierdonck, Candice Chapouly, Yang Yu, Gangjian Qin, et al.. Gli3 Regulation of Myogenesis Is Necessary for Ischemia-Induced Angiogenesis. Circulation Research, American Heart Association, 2013, 113 (10), pp.1148 - 1158. ⟨10.1161/CIRCRESAHA.113.301546⟩. ⟨inserm-01777743⟩

Share

Metrics

Record views

116