Distribution of TGF-β Isoforms and Signaling Intermediates in Corneal Fibrotic Wound Repair
Distribution of TGF-β Isoforms and Signaling Intermediates in Corneal Fibrotic Wound Repair
复制标题
DOI：
10.1002/jcb.22277
复制
发表时间：
2009-10-01
影响因子：
4
通讯作者：
Jung, Jae-Chang
中科院分区：
文献类型：
--
作者：
Huh, Man-Il;Kim, Yeoun-Hee;Jung, Jae-Chang
在这项研究中，时间和空间分布的三个TGF-β亚型及其下游信号通路，包括pSmad 2和p38 MAPK纤维化伤口修复过程中进行了检查。在正常鸡角膜中，在Bowman层（BL）中检测到微弱的TGF-β 1、TGF-β 2和TGF-β 3。在愈合的角膜，TGF-β 1主要沉积在纤维蛋白凝块和未受伤的BL。TGF-β 2在愈合的上皮细胞和内皮细胞以及许多活跃的成纤维细胞/肌成纤维细胞中高度表达。TGF-β 3主要在基底上皮细胞的非创伤区域检测到。α-平滑肌肌动蛋白（α-SMA）最初在第3天出现在修复基质的后部区域，并且在第7天在整个愈合基质中检测到。值得注意的是，到第14天，愈合基质的中心区域不存在a-SMA，其染色模式与TGF-β 2和p38 MAPK的染色模式相似。pSmad 2主要在成纤维细胞中表达。在正常角膜中，层粘连蛋白主要表达于上皮基底膜（BM）和后弹力层（DM）。与伤口区域中BM的重建相反，尽管内皮层再生，但DM未被修复，表明在第14天高水平的TGF-β 2被释放到愈合基质的后部区域。在第14天来自愈合角膜的培养的修复基质细胞和TGF-β 2处理的正常基质细胞中显示的高水平的α-SMA染色通过p38 MAPK抑制显著降低。总的来说，这项研究表明，TGF-β 2介导的肌成纤维细胞转化介导的，至少部分，在体内的p38 MAPK途径。J.细胞。108：476-488，2009. (C)2009年威利-利斯。Inc.
In this study, temporal and spatial distribution of three TGF-beta isoforms and their downstream signaling pathways including pSmad2 and p38MAPK were examined during fibrotic wound repair. In normal chick corneas, TGF-beta 1, -2, and -3 were weakly detected in Bowman's layer (BL). In healing corneas, TGF-beta 1 was primarily deposited in the fibrin clot and the unwounded BL. TGF-beta 2 was highly expressed in healing epithelial and endothelial cells, and numerous active fibroblasts/myofibroblasts. TGF-beta 3 was mainly detected in the unwound region of basal epithelial cells. alpha-Smooth muscle actin (alpha-SMA) was initially appeared in the posterior region of repairing stroma at day 3, and was detected in the entire healing stroma by day 7. Notably, a-SMA was absent in the central region of healing stroma by day 14, and its staining pattern was similar to those of TGF-beta 2 and p38MAPK. By contrast, pSmad2 was mainly detected in the fibroblasts. In normal cornea, laminin was mainly detected in both epithelial basement membrane (BM) and Descemet's membrane (DM). By contrast to reconstitution of the BM in the wound region, the DM was not repaired although endothelial layer was regenerated, indicating that high levels of TGF-beta 2 were released into the posterior region of healing stroma on day 14. High levels of a-SMA staining, shown in cultured repair stromal cells from healing corneas on day 14 and in TGF-beta 2 treated normal stromal cells, were significantly reduced by p38MAPK inhibition. Collectively, this study suggests that TGF-beta 2-mediated myofibroblast transformation is mediated, at least partly, by the p38MAPK pathway in vivo. J. Cell. Biochem. 108: 476-488, 2009. (C) 2009 Wiley-Liss. Inc.