PGC-1α modulates necrosis, inflammatory response, and fibrotic tissue formation in injured skeletal muscle

被引：37

作者：

Dinulovic, Ivana ^{[1
]}

Furrer, Regula ^{[1
]}

Di Fulvio, Sabrina ^{[1
]}

Ferry, Arnaud ^{[2
,3
]}

Beer, Markus ^{[1
]}

Handschin, Christoph ^{[1
]}

机构：

[1] Univ Basel, Biozentrum, Klingelbergstr 50-70, CH-4056 Basel, Switzerland

[2] Inst Myol, UPMC UM76, CNRS UMR7215, Therapie Malad Muscle Strie INSERM U974, 47 Bld Hop, F-75013 Paris, France

[3] Univ Paris 05, GH Pitie Salpetriere, 47 Bld Hop, F-75013 Paris, France

来源：

SKELETAL MUSCLE | 2016年 / 6卷

基金：

瑞士国家科学基金会;

关键词：

PGC-1; alpha; Regeneration; Inflammation; Fibrosis; Macrophages; Necrosis; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; PGC-1; COACTIVATORS; NEUROMUSCULAR-JUNCTION; ECCENTRIC EXERCISE; NULL MICE; REGENERATION; EXPRESSION; FIBROSIS; DISEASE; REPAIR;

D O I：

10.1186/s13395-016-0110-x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Background: Skeletal muscle tissue has an enormous regenerative capacity that is instrumental for a successful defense against muscle injury and wasting. The peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) exerts therapeutic effects in several muscle pathologies, but its role in damage-induced muscle regeneration is unclear. Methods: Using muscle-specific gain-and loss-of-function models for PGC-1 alpha in combination with the myotoxic agent cardiotoxin (CTX), we explored the role of this transcriptional coactivator in muscle damage and inflammation. Results: Interestingly, we observed PGC-1 alpha-dependent effects at the early stages of regeneration, in particular regarding macrophage accumulation and polarization from the pro-inflammatory M1 to the anti-inflammatory M2 type, a faster resolution of necrosis and protection against the development of fibrosis after multiple CTX-induced injuries. Conclusions: PGC-1 alpha exerts beneficial effects on muscle inflammation that might contribute to the therapeutic effects of elevated muscle PGC-1 alpha in different models of muscle wasting.

引用

页数：11

共 39 条

[1]

Muscle-specific expression of PPARγ coactivator-1α improves exercise performance and increases peak oxygen uptake [J].