Expression of myogenic regulatory factors and myo-endothelial remodeling in sporadic inclusion body myositis

详细信息    查看全文

• 作者：Julia V. Wanschitz^a ; ^d ; ^{julia.wanschitz@i-med.ac.at} ; Odile Dubourg^f ; Emmanuelle Lacene^d ; Michael B. Fischer^b ; Romana Hö ; ftberger^c ; Herbert Budka^c ; Norma B. Romero^d ; Bruno Eymard^d ; ^e ; Serge Herson^d ; ^g ; Gillian S. Butler-Browne^d ; Thomas Voit^d ; Olivier Benveniste^d ; ^g
• 关键词：Sporadic inclusion body myositis ; Myogenesis ; Satellite cells ; Microvascularization
• 刊名：Neuromuscular Disorders
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：23
• 期：1
• 页码：75-83
• 全文大小：1090 K

文摘

Muscle repair relies on coordinated activation and differentiation of satellite cells, a process that is unable to counterbalance progressive degeneration in sporadic inclusion body myositis (s-IBM). To explore features of myo regeneration, the expression of myogenic regulatory factors Pax7, MyoD and Myogenin and markers of regenerating fibers was analyzed by immunohistochemistry in s-IBM muscle compared with polymyositis, dermatomyositis, muscular dystrophy and age-matched controls. In addition, the capillary density and number of interstitial CD34⁺ hematopoietic progenitor cells was determined by double-immunoflourescence staining. Satellite cells and regenerating fibers were significantly increased in s-IBM similar to other inflammatory myopathies and correlated with the intensity of inflammation (R > 0.428). Expression of MyoD, visualizing activated satellite cells and proliferating myoblasts, was lower in s-IBM compared to polymyosits. In contrast, Myogenin a marker of myogenic cell differentiation was strongly up-regulated in s-IBM muscle. The microvascular architecture in s-IBM was distorted, although the capillary density was normal. Notably, CD34⁺ hematopoietic cells were significantly increased in the interstitial compartment. Our findings indicate profound myo-endothelial remodeling of s-IBM muscle concomitant to inflammation. An altered expression of myogenic regulatory factors involved in satellite cell activation and differentiation, however, might reflect perturbations of muscle repair in s-IBM.