Skip to Main content Skip to Navigation
Journal articles

Hedgehog-Dependent Regulation of Angiogenesis and Myogenesis Is Impaired in Aged Mice

Abstract : OBJECTIVE: The purpose of this study is to further document alteration of signal transduction pathways, more particularly of hedgehog (Hh) signaling, causing impaired ischemic muscle repair in old mice. APPROACH AND RESULTS: We used 12-week-old (young mice) and 20- to 24-month-old C57BL/6 mice (old mice) to investigate the activity of Hh signaling in the setting of hindlimb ischemia-induced angiogenesis and skeletal muscle repair. In this model, delayed ischemic muscle repair observed in old mice was associated with an impaired upregulation of Gli1. Sonic Hh expression was not different in old mice compared with young mice, whereas desert Hh (Dhh) expression was downregulated in the skeletal muscle of old mice both in healthy and ischemic conditions. The rescue of Dhh expression by gene therapy in old mice promoted ischemia-induced angiogenesis and increased nerve density; nevertheless, it failed to promote myogenesis or to increase Gli1 mRNA expression. After further investigation, we found that, in addition to Dhh, smoothened expression was significantly downregulated in old mice. We used smoothened haploinsufficient mice to demonstrate that smoothened knockdown by 50% is sufficient to impair activation of Hh signaling and ischemia-induced muscle repair. CONCLUSIONS: The present study demonstrates that Hh signaling is impaired in aged mice because of Dhh and smoothened downregulation. Moreover, it shows that hegdehog-dependent regulation of angiogenesis and myogenesis involves distinct mechanisms.
Document type :
Journal articles
Complete list of metadata
Contributor : LAURE PENIGAUD Connect in order to contact the contributor
Submitted on : Wednesday, April 25, 2018 - 9:37:52 AM
Last modification on : Wednesday, September 9, 2020 - 3:01:01 AM

Links full text




Marie-Ange Renault, Fanny Robbesyn, Candice Chapouly, Qinyu yao, Soizic Vandierdonck, et al.. Hedgehog-Dependent Regulation of Angiogenesis and Myogenesis Is Impaired in Aged Mice. Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2013, 33 (12), pp.2858 - 2866. ⟨10.1161/ATVBAHA.113.302494⟩. ⟨inserm-01777723⟩



Record views