Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy
Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy
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DOI：
10.1016/j.jns.2007.09.043
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发表时间：
2008-04-15
影响因子：
4.4
通讯作者：
Tsuchiya, Shigeru
中科院分区：
文献类型：
--
作者：
Sun, Guilian;Haginoya, Kazuhiro;Tsuchiya, Shigeru
营养不良的肌肉如何被纤维化组织取代的详细过程尚不清楚。本研究通过检测结缔组织生长因子（CTGF）在正常和营养不良人体肌肉中的免疫定位和mRNA表达，旨在阐明CTGF在肌肉营养不良中的病理生理功能。采用抗ctgf多克隆抗体对杜氏肌营养不良症（DMD）、贝克肌营养不良症、先天性肌营养不良症、脊髓性肌萎缩症、先天性肌病患者的冷冻肌肉活检进行分析。采用逆转录聚合酶链反应（RT-PCR）评价CTGF mRNA在营养不良肌肉中的表达。在正常肌肉中，神经肌肉连接处和血管呈CTGF免疫阳性，这表明CTGF在这些部位具有生理作用。在营养不良肌肉中，CTGF免疫反应性局限于肌纤维基底层、再生纤维和间质。三重免疫标记显示，活化的成纤维细胞CTGF和转化生长因子- β (tgf - β 1)免疫阳性。RT-PCR分析显示，DMD患者肌肉中CTGF mRNA水平升高。TGF-beta1和CTGF在活化成纤维细胞中的共定位表明，TGF-beta1通过旁分泌/自分泌机制调节CTGF的表达。综上所述，tgf - β - ctgf通路可能在肌营养不良中常见的纤维化中发挥作用。(C) 2007 Elsevier B.V.版权所有
The detailed process of how dystrophic muscles are replaced by fibrotic tissues is unknown. In the present study, the immunolocalization and mRNA expression of connective tissue growth factor (CTGF) in muscles from normal and dystrophic human muscles were examined with the goal of elucidating the pathophysiological function of CTGF in muscular dystrophy. Biopsies of frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, congenital muscular dystrophy, spinal muscular atrophy, congenital myopathy were analyzed using anti-CTGF polyclonal antibody. Reverse transcription-polymerase chain reaction (RT-PCR) was also performed to evaluate the expression of CTGF mRNA in dystrophic muscles. In normal muscle, neuromuscular junctions and vessels were CTGF-immunopositive, which suggests a physiological role for CTGF in these sites. In dystrophic muscle, CTGF immunoreactivity was localized to muscle fiber basal lamina, regenerating fibers, and the interstitium. Triple immunolabeling revealed that activated fibroblasts were immunopositive for CTGF and transforming growth factor-betal (TGF-beta1). RT-PCR analysis revealed increased levels of CTGF mRNA in the muscles of DMD) patients. Co-localization of TGF-beta1 and CTGF in activated fibroblasts suggests that CTGF expression is regulated by TGF-beta1 through a paracrine/autocrine mechanism. In conclusion, TGF-beta1-CTGF pathway may play a role in the fibrosis that is commonly observed in muscular dystrophy. (C) 2007 Elsevier B.V. All rights reserved.