Cellular sources of transforming growth factor-beta isoforms in early and chronic radiation enteropathy.
Cellular sources of transforming growth factor-beta isoforms in early and chronic radiation enteropathy.
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DOI：
10.1016/s0002-9440(10)65741-0
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发表时间：
1998-11
期刊：
影响因子：
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通讯作者：
Junru Wang;Huaien Zheng;C. Sung;K. Richter;M. Hauer-Jensen
中科院分区：
文献类型：
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作者：
Junru Wang;Huaien Zheng;C. Sung;K. Richter;M. Hauer-Jensen
三种哺乳动物转化生长因子-β亚型(转化生长因子-β1、转化生长因子-β2和转化生长因子-β3)在辐射诱导的肠道和其他器官纤维化中的作用不同。此外，转化生长因子-β作用的组织特异性可能是由于产生和/或激活的时间或空间变化所致。本研究检测了放射性肠病发展过程中转化生长因子-β基因表达的细胞类型的变化与转化生长因子-β免疫反应和组织病理损伤的关系。用0、12或21GyX射线单次照射大鼠4厘米长的小肠环行局部照射。照射后2周和26周分别取假照射组和照射组大鼠小肠。地高辛标记的核糖核酸探针原位杂交鉴定表达转化生长因子-β1、转化生长因子-β2和转化生长因子-β3转录本的细胞。计算机图像分析检测肠壁转化生长因子-β免疫反应性，定量组织病理学评价结构放射性损伤。正常肠上皮细胞表达三种转化生长因子-β亚型的转录本。照射后2周，再生隐窝、炎性细胞、平滑肌细胞和间皮细胞的转化生长因子-β-1表达增强，转化生长因子-β-2和转化生长因子-β3表达减弱。照射后26周，转化生长因子-β-2和转化生长因子-β-3的表达均恢复正常。相反，转化生长因子-β1在慢性纤维化区域的平滑肌、间皮细胞、内皮细胞和成纤维细胞中的表达仍较高。与细胞外基质相关的转化生长因子-β-1免疫反应在两个观察时间段均显著增加，而转化生长因子-β-2和转化生长因子-β-3免疫反应在照射后变化不大。肠辐射损伤与再生上皮中所有三种转化生长因子-β亚型的过度表达有关。放射性肠病还与转化生长因子-β1的细胞来源从上皮细胞向参与慢性纤维化发病机制的细胞的持续转移有关。转化生长因子-β-2和转化生长因子-β-3没有表现出长期一致的变化。转化生长因子-β-1是放射性肠病的主要亚型，在放射性肠病的发病机制中可能比转化生长因子-β-2和转化生长因子-β-3更重要。
The three mammalian transforming growth factor (TGF)-β isoforms (TGF-β1, TGF-β2, and TGF-β3) differ in their putative roles in radiation-induced fibrosis in intestine and other organs. Furthermore, tissue specificity of TGF-β action may result from temporal or spatial changes in production and/or activation. The present study examined shifts in the cell types expressing TGF-β mRNA relative to TGF-β immunoreactivity and histopathological injury during radiation enteropathy development. A 4-cm loop of rat small intestine was locally exposed to 0, 12, or 21-Gy single doses of x-irradiation. Sham-irradiated and irradiated intestine were procured 2 and 26 weeks after irradiation. Cells expressing the TGF-β1, TGF-β2, or TGF-β3 transcripts were identified by in situ hybridization with digoxigenin-labeled riboprobes. Intestinal wall TGF-β immunoreactivity was measured using computerized image analysis, and structural radiation injury was assessed by quantitative histopathology. Normal intestinal epithelium expressed transcripts for all three TGF-β isoforms. Two weeks after irradiation, regenerating crypts, inflammatory cells, smooth muscle cells, and mesothelium exhibited increased TGF-β1 expression and, to a lesser degree, TGF-β2 and TGF-β3 expression. Twenty-six weeks after irradiation, TGF-β2 and TGF-β3 expression had returned to normal. In contrast, TGF-β1 expression remained elevated in smooth muscle, mesothelium, endothelium, and fibroblasts in regions of chronic fibrosis. Extracellular matrix-associated TGF-β1 immunoreactivity was significantly increased at both observation times, whereas, TGF-β2 and TGF-β3 immunoreactivity exhibited minimal postradiation changes. Intestinal radiation injury is associated with overexpression of all three TGF-β isoforms in regenerating epithelium. Radiation enteropathy was also associated with sustained shifts in the cellular sources of TGF-β1 from epithelial cells to cells involved in the pathogenesis of chronic fibrosis. TGF-β2 and TGF-β3 did not exhibit consistent long-term changes. TGF-β1 appears to be the predominant isoform in radiation enteropathy and may be more important in the mechanisms of chronicity than TGF-β2 and TGF-β3.