Temporal and spatial distribution of TGF-β isoforms and signaling intermediates in corneal regenerative wound repair
Temporal and spatial distribution of TGF-β isoforms and signaling intermediates in corneal regenerative wound repair
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DOI：
10.14670/hh-24.1405
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发表时间：
2009-11-01
影响因子：
2
通讯作者：
Jung, Jae-Chang
中科院分区：
文献类型：
--
作者：
Huh, Man-IL;Chang, Yongmin;Jung, Jae-Chang
本研究通过免疫组织化学方法分析了TGF-β亚型和激活的pSmad 2和p38 MAPK在上皮清创伤口修复过程中的时空表达。正常角膜显示低水平的TGF-β s染色。创伤后，Bowman层（BL）中TGF-β 1表达强烈。TGF-β 3表达仅限于再生和未受伤区域的基底细胞，在迁移的上皮细胞、基质细胞或内皮细胞中未检测到。此外，TGF-β 3处理刺激了培养的上皮细胞的增殖。我们目前的研究结果似乎表明，TGF-β 3信号可能是上皮细胞增殖所必需的。TGF-β 2在迁移和增殖的上皮细胞、伤口边缘的许多活跃迁移的成纤维细胞、内皮细胞和后弹力膜（DM）中表达强烈。pSmad 2和p38 MAPK在基底层上皮细胞中均有表达，但pSmad 2阳性细胞与PCNA阳性细胞共定位。因此，似乎pSmad 2信号可能影响愈合角膜中的上皮细胞增殖。pSmad 2和p38 MAPK在内皮细胞中也有表达。有趣的是，在第2天的早期伤口愈合中，整个基质中的许多活性成纤维细胞表达核pSmad 2，但几乎不表达细胞质p38 MAPK。总的来说，时间/空间上调和分布的三个TGF-β亚型，以及Smad 2和p38 MAPK的协同激活，似乎是一个关键方面的再生角膜伤口愈合的小鸡。
The present study analyzed the temporal and spatial expression of TGF-beta isoforms and activated pSmad2 and p38MAPK during epithelial debridement wound repair, using chick cornea by immunohistochemistry. Normal corneas showed low-level TGF-beta s staining. Following wounding, TGF-beta 1 expression was strong in the Bowman's layer (BL). TGF-beta 3 expression was confined to basal cells in the regenerating and unwounded regions, and was not detected in migrating epithelial, stromal or endothelial cells. In addition, TGF-beta 3 treatment stimulated the proliferation of cultured epithelial cells. Our present findings seem to suggest that the TGF-beta 3 signal may be required for epithelial cell proliferation. TGF-beta 2 expression was strong in migrating and proliferating epithelial cells, many active migrating fibroblasts at the wound edge, endothelial cells and Descemet's membrane (DM). Although both nuclear pSmad2 and p38MAPK staining was observed in many basal epithelial cells, pSmad2 positive cells were co-localized with PCNA positive cells. Therefore, it seems likely that the pSmad2 signal may affect epithelial cell proliferation in healing corneas. Both pSmad2 and p38MAPK expression were also observed in endothelial cells. Interestingly, many active fibroblasts over the whole stroma in early wound healing at day 2 expressed nuclear pSmad2, but little if any cytoplasmic p38MAPK. Collectively, temporal/spatial up-regulation and distribution of the three TGF-beta isoforms, as well as concerted activation of both Smad2 and p38MAPK, appears to be a key aspect of regenerative corneal wound healing in the chick.