Myofibroblasts in proliferative diabetic retinopathy can originate from infiltrating fibrocytes and through endothelial-to-mesenchymal transition (EndoMT)
Myofibroblasts in proliferative diabetic retinopathy can originate from infiltrating fibrocytes and through endothelial-to-mesenchymal transition (EndoMT)
复制标题
DOI：
10.1016/j.exer.2015.01.023
复制
发表时间：
2015-03-01
影响因子：
3.4
通讯作者：
Struyf, Sofie
中科院分区：
文献类型：
--
作者：
Abu El-Asrar, Ahmed M.;De Hertogh, Gert;Struyf, Sofie
表达A-平滑肌肌动蛋白（α-SMA）的肌纤维细胞是纤维化的关键细胞介体。来自增殖性糖尿病性视网膜病（PDR）患者的纤维血管头膜的特征是大量肌纤维细胞积累。我们探讨了以下假设：通过内皮间充质转变（endomt）和/或骨髓衍生的循环纤维细胞增殖的内皮细胞增殖，从而有助于PDR膜中膜中存在的肌纤维细胞群。通过免疫组织化学研究了来自14例PDR患者的14例PDR患者的前膜。所有膜均包含表达内皮细胞标记CD31的新膜。 CD31（+）内皮细胞共表达成纤维细胞/成肌纤维细胞标志物成纤维细胞特异性蛋白-1（FSP-1）和α-SMA，这指示了胚胎的发生。在基质中，检测到表达FSP-1，Alpha-SMA，白细胞常见抗原CD45和脊髓细胞标记CD11b的细胞。双重标记显示CD45与FSP-1和Alpha-SMA的共定位以及CD11b与α-SMA和基质金属蛋白酶9的共定位，证明存在浸润纤维细胞。此外，我们研究了暴露于转化生长因子-Beta 1（TGF-BETA 1），结缔组织生长因子（CTGF）和促炎细胞因子毒素细胞因子beta（ILILILIL-1 beta）（ILILILILIL-1），调查了人视网膜微血管内皮细胞中发生的表型变化-1β）和肿瘤坏死因子-Alpha（TNF-Alpha）。视网膜微血管内皮细胞改变了细胞因子暴露后的形态，失去了内皮细胞标记物（内皮一氧化氮合酶和血管内皮 - 钙粘着蛋白）的表达，并开始表达间质标记物（钙蛋白，snail，snail，transgelin and transgelin and fsp-1）。这些结果表明，内皮细胞以及循环纤维细胞可能会在糖尿病眼中区分成肌纤维细胞，并有助于PDR中的病理纤维化。 （c）2015 Elsevier Ltd.保留所有权利。
Myofibroblasts expressing a-smooth muscle actin (alpha-SMA) are the key cellular mediator of fibrosis. Fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endothelial cells via endothelial-to-mesenchymal transition (EndoMT) and/or bone marrow-derived circulating fibrocytes contribute to the myofibroblast population present in PDR epiretinal membranes. Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. All membranes contained neovessels expressing the endothelial cell marker CD31. CD31(+) endothelial cells co-expressed the fibroblast/myofibroblast markers fibroblast-specific protein-1 (FSP-1) and alpha-SMA, indicative for the occurrence of endoMT. In the stroma, cells expressing FSP-1, alpha-SMA, the leukocyte common antigen CD45, and the myelomonocytic marker CD11b were detected. Double labeling showed co-localization of CD45 with FSP-1 and alpha-SMA and co-localization of CD11b with alpha-SMA and matrix metalloproteinase-9, demonstrating the presence of infiltrating fibrocytes. In addition, we investigated the phenotypic changes that take place in human retinal microvascular endothelial cells following exposure to transforming growth factor-beta 1 (TGF-beta 1), connective tissue growth factor (CTGF) and the proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). Retinal microvascular endothelial cells changed morphology upon cytokine exposure, lost the expression of endothelial cell markers (endothelial nitric oxide synthase and vascular endothelial-cadherin) and started to express mesenchymal markers (calponin, snail, transgelin and FSP-1). These results suggest that endothelial cells as well as circulating fibrocytes may differentiate into myofibroblasts in the diabetic eye and contribute to pathologic fibrosis in PDR. (C) 2015 Elsevier Ltd. All rights reserved.