Epithelial Mesenchymal Transition in Human Ocular Chronic Graft-Versus-Host Disease
Epithelial Mesenchymal Transition in Human Ocular Chronic Graft-Versus-Host Disease
复制标题
DOI：
10.2353/ajpath.2009.090318
复制
发表时间：
2009-12-01
影响因子：
6
通讯作者：
Tsubota, Kazuo
中科院分区：
文献类型：
--
作者：
Ogawa, Yoko;Shimmura, Shigeto;Tsubota, Kazuo
眼表和泪腺的慢性移植物抗宿主病(CGVHD)是异基因骨髓移植后发生的一种威胁视力的疾病。在这项研究中，我们使用免疫组织化学和电子显微镜来研究上皮间充质转化(EMT)是否参与了眼部cGVHD的发病。我们检测到E-钙粘附素的下调和β-连环素从细胞间连接到cGVHD结膜基底层上皮和泪腺肌上皮的胞浆和胞核的移位。值得注意的发现包括EMT的诱导物Snail在眼部cGVHD上皮细胞核中的表达。纤维化标志物热休克蛋白47、α-平滑肌肌动蛋白和成纤维细胞特异性蛋白-1在眼部移植物移植物抗宿主病上皮细胞中过表达。此外，结膜基底层上皮细胞的标志物p63在基板下结膜下细胞的胞核中也有表达。CGVRD上皮下和细胞质内可见基底膜断裂和胶原束改变。相反，这些观察很少在正常结膜和干燥综合征泪腺上皮中观察到。这些发现共同表明，眼部cGVHD上皮细胞获得了间充质表型和向上皮下基质迁移的能力。我们的发现提示EMT可能是cGVHD患者结膜和泪腺纤维化的部分原因。(Am J Pathol2009175：23722381；DOI：10.2353/ajpath.2009.090318)
Chronic graft-versus-host disease (cGVHD) of the ocular surface and lacrimal gland is a vision-threatening condition that occurs after allogencic bone marrow transplantation. in this study, we used imunohistochemistry and electron microscopy to investigate whether epithelial mesenchymal transition (EMT) contributed to the pathogenesis of ocular cGVHD. We detected down-regulation of E-cadherin and translocation of beta-catenin from the intercellular junction to the cytoplasm and nucleus of cGVHD conjunctival basal epithelia and lacrimal gland myoepithelia. Notable findings included expression of Snail, an inducer of EMT, in the nucleus of ocular cGVHD epithelia. The fibrosis markers heat shock protein 47, a-smooth muscle actin, and fibroblast specific protein-1 were overexpressed in ocular cGVHD epithelia. In addition, p63, a marker of conjunctival basal epithelia, was observed in the nuclei of subconjunctival cells beneath disrupted basal lamina. Disrupted basal lamina and the presence of altered collagen bundles were observed in the cytoplasm and beneath cGVRD epithelia. in contrast, these observations were rarely observed in the normal conjunctiva and in Sjogren's syndrome lacrimal gland epithelia. These findings together indicate that ocular cGVHD epithelia gain the mesenchymal phenotype and the capacity to migrate into the subepithelial stroma. Our findings suggest that EMT may be partially responsible for the conjunctival and lacrimal gland fibrosis found in patients with cGVHD. (Am J Pathol 2009, 175:2372-2381; DOI: 10.2353/ajpath.2009.090318)