Role of transforming growth factor-β1 in the process of fibrosis of denervated skeletal muscle

Role of transforming growth factor-β1 in the process of fibrosis of denervated skeletal muscle
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转化生长因子-β1在失神经骨骼肌纤维化过程中的作用

DOI:
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发表时间:
2011
期刊:
Journal of Huazhong University of Science and Technology. Medical Sciences
影响因子:
--
通讯作者:
Zhenbing Chen
Zhenbing Chen
中科院分区:
--
文献类型:
--
作者:
Fanbin Meng;Jiang;Liu Juan;Wang Yang;Yu;Yan;Liping Tao;Zhenbing Chen

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为了探讨转化生长因子-β1(transforminggrowthfactor-β 1,TGF-β1)在失神经骨骼肌纤维化中的生物学作用,我们建立了SD大鼠坐骨神经损伤模型,分离失神经腓肠肌进行分析。在术后不同时间点,采用多种方法对失神经肌肉进行检查。Masson三色染色显示失神经骨骼肌的形态学改变。定量RT-PCR检测到神经损伤后TGF-β1 mRNA表达迅速增加。结果发现,TGF-β1 mRNA表达在术后1周出现高峰。神经损伤模型中I型胶原(COL I)mRNA的表达也上调,并在损伤后两周达到最高水平。免疫印迹显示TGF-β1和COL I在失神经肌肉中的蛋白表达模式相似。此外,我们还发现腓肠肌纤维面积随着骨骼肌纤维化程度的加重而沿着逐渐减小。有趣的是,这种病理变化可以通过局部注射TGF-β1抗体至少部分地预防,这可以通过抑制TGF-β1的功能来减少COL I的产生。综上所述,本研究证实了TGF-β1在失神经骨骼肌中的表达显著增加,这可能在神经切断后骨骼肌纤维化过程中起重要作用。
SummaryIn order to investigate the biological function of transforming growth factor-β1 (TGF-β1) during fibrosis in denervated skeletal muscle, we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis. At different time points after operation, denervated muscle was examined by several methods. Masson trichrome staining showed morphological changes of denervated skeletal muscle. Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury. It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation. The expression of collagen I (COL I) mRNA was up-regulated in the nerve injury model as well, and reached highest level two weeks post-injury. Immunoblot revealed similar expression pattern of TGF-β1 and COL I in denervated muscles at protein level. In addition, we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis. Interestingly, this pathological change could be prevented, at least partly, by local injection of TGF-β1 antibodies, which could be contributed to the reduced production of COL I by inhibiting function of TGF-β1. Taken together, in this study, we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle, which might play a crucial role during muscle fibrosis after nerve transection.
DOI: 10.2353/ajpath.2009.080509
发表时间: 2009-02
期刊: The American journal of pathology
影响因子: --
作者:
William Wang;H. Pan;K. Murray;B. Jefferson;Yong Li
通讯作者: William Wang;H. Pan;K. Murray;B. Jefferson;Yong Li
DOI: 10.1016/s0002-9440(10)61185-6
发表时间: 2005-10-01
影响因子: 6
作者:
Wen, XY;Li, YJ;Liu, YH
通讯作者: Liu, YH