Sun Guilian, Haginoya Kazuhiro, Wu Yanling, Chiba Yoko, Nakanishi Tohru, Onuma Akira, Sato Yuko, Takigawa Masaharu, Iinuma Kazuie, Tsuchiya Shigeru
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
J Neurol Sci. 2008 Apr 15;267(1-2):48-56. doi: 10.1016/j.jns.2007.09.043. Epub 2007 Nov 9.
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-beta1 (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.
营养不良性肌肉如何被纤维化组织替代的详细过程尚不清楚。在本研究中，检测了正常和营养不良性人类肌肉中结缔组织生长因子（CTGF）的免疫定位和mRNA表达，目的是阐明CTGF在肌肉营养不良中的病理生理功能。使用抗CTGF多克隆抗体分析了杜氏肌营养不良症（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标本。还进行了逆转录-聚合酶链反应（RT-PCR）以评估CTGF mRNA在营养不良性肌肉中的表达。在正常肌肉中，神经肌肉接头和血管CTGF免疫阳性，这表明CTGF在这些部位具有生理作用。在营养不良性肌肉中，CTGF免疫反应定位于肌纤维基膜、再生纤维和间质。三重免疫标记显示活化的成纤维细胞对CTGF和转化生长因子-β1（TGF-β1）免疫阳性。RT-PCR分析显示DMD患者肌肉中CTGF mRNA水平升高。TGF-β1和CTGF在活化成纤维细胞中的共定位表明CTGF表达受TGF-β1通过旁分泌/自分泌机制调节。总之，TGF-β1-CTGF途径可能在肌肉营养不良中常见的纤维化过程中起作用。
