Muscle Weakness and Fibrosis Due to Cell Autonomous and Non-cell Autonomous Events in Collagen VI Deficient Congenital Muscular Dystrophy

详细信息    查看全文

• 作者：Satoru Noguchi^a ; ^b ; ^{noguchi@ncnp.go.jp} ; Megumu Ogawa^a ; May Christine Malicdan^c ; ^d ; Ikuya Nonaka^a ; Ichizo Nishino^a ; ^b
• 关键词：Collagen ; Fibrosis ; IGF-1 ; Mesenchymal ; Mouse ; Muscular dystrophy ; Skeletal muscles ; Weakness
• 刊名：EBioMedicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：15
• 期：Complete
• 页码：193-202
• 全文大小：2670 K
• 卷排序：15

文摘

Collagen VI muscular dystrophy mouse shows small muscle size and endomysial fibrosis. Insufficient IGF-1 signaling in Col6a1GT/GT is responsible for decreased myofiber numbers during perinatal muscle growth. Overactivation of MPCs in Col6a1GT/GT largely contributes to fibrosis, possibly explaining the phenotype of human patients.Congenital muscular dystrophy with collagen VI deficiency shows specific muscle pathology characterized by fiber size variation and increased interstitial fibrosis and adipogenesis. We show two mechanistic events in the model mouse, an impaired muscle growth during perinatal due to insufficient IGF-1 signaling, and an endomysial fibrosis by overactivation of muscle-residential mesenchymal progenitor cells. This overactivation induces the dysregulated muscle niche, which results in specific pathology in collagen VI deficient muscular dystrophy.