Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression
Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression
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DOI：
10.1016/s0360-3016(02)04601-1
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发表时间：
2003-06-01
影响因子：
7
通讯作者：
Aigueperse, J
中科院分区：
文献类型：
--
作者：
Vozenin-Brotons, MC;Milliat, F;Aigueperse, J
目的：探讨新型纤维化细胞因子结缔组织生长因子（CTGF）在肠道放射性纤维化中的表达，并表征参与CTGF合成和胶原沉积的间充质细胞亚型。 方法和材料：16名盆腔恶性肿瘤放疗后发生放射性肠炎的患者和6名组织学正常肠道的患者进入研究。采用免疫组织化学、蛋白质印迹分析和实时逆转录聚合酶链反应来研究 CTGF 表达以及其他已知的放射纤维化标记物：促纤维化细胞因子转化生长因子 (TGF)-β1 和成纤维细胞分化的表型标记物 α-sm 肌动蛋白 (A)、波形蛋白 (V) 和结蛋白 (D)。最后，通过天狼星红染色和比色测定来测量胶原蛋白的积累。结果：放射性肠炎的特点是肠壁内胶原蛋白含量增加。与健康肠道相比，放射性肠炎中的 CTGF 免疫反应性、蛋白质和 mRNA 水平升高。相反，与健康肠道相比，放射性肠炎中TGF-β1 mRNA水平没有观察到升高，而TGF-β蛋白水平在放射性肠炎中略有升高。在具有成纤维细胞表型（V+/D-/A(-)）和肌成纤维细胞表型（V+/D-/+/A(+)）的活化间充质细胞的细胞外基质和亚型中发现CTGF免疫反应性和胶原沉积的共定位。结论：与成纤维细胞/肌成纤维细胞积累和胶原沉积相关的CTGF蛋白和mRNA水平的增加是纤维化信号的一部分参与晚期肠道放射性纤维化的持续存在。 (C) 2003 爱思唯尔公司。
Purpose: To investigate the expression of a new fibrogenic cytokine the connective tissue growth factor (CTGF) in intestinal radiation fibrosis and to characterize the mesenchymal cell subtypes involved in CTGF synthesis and collagen deposition.Methods and Materials: Sixteen patients with radiation enteritis that occurred after radiotherapy for pelvic malignancies and 6 with histologically normal bowel entered the study. Immunohistochemistry, Western blot analysis, and real-time reverse transcriptase-polymerase chain reaction were performed to study CTGF expression, along with other known markers of radiation fibrosis: the pro-fibrogenic cytokine transforming growth factor (TGF)-beta1 and phenotypic markers of the fibroblast differentiation the alpha-sm actin (A), vimentin (V), and desmin (D). Finally, the collagen accumulation was measured by Sirius red staining and colorimetric assay.Results: Radiation enteritis was characterized by increased collagen content within the intestinal wall. CTGF immunoreactivity, protein, and mRNA level were increased in radiation enteritis compared with the healthy bowel. On the contrary, no increase of the TGF-beta1 mRNA level was observed in radiation enteritis compared with healthy bowel, and the level of TGF-beta protein was slightly increased in radiation enteritis. A co-localization of CTGF immunoreactivity and collagen deposition was found in the extracellular matrix and subtypes of activated mesenchymal cells with a fibroblast phenotype (V+/D-/A(-)) and myofibroblast phenotype (V+/D-/+/A(+)).Conclusion: The increased level of CTGF protein and mRNA associated with the accumulation of fibroblasts/myofibroblasts and collagen deposition were parts of the fibrogenic signals involved in the persistence of late intestinal radiation fibrosis. (C) 2003 Elsevier Inc.