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αvβ3 整联蛋白的过表达和激活可使人类小梁细胞中 TGFβ2 信号转导呈现差异化。

Overexpression and Activation of αvβ3 Integrin Differentially Affects TGFβ2 Signaling in Human Trabecular Meshwork Cells.

机构信息

Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI 53705, USA.

Ophthalmology & Visual Sciences, University of Wisconsin, Madison, WI 53705, USA.

出版信息

Cells. 2021 Jul 29;10(8):1923. doi: 10.3390/cells10081923.

DOI:10.3390/cells10081923
PMID:34440692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8394542/
Abstract

Studies from our laboratory have suggested that activation of αvβ3 integrin-mediated signaling could contribute to the fibrotic-like changes observed in primary open angle glaucoma (POAG) and glucocorticoid-induced glaucoma. To determine how αvβ3 integrin signaling could be involved in this process, RNA-Seq analysis was used to analyze the transcriptomes of immortalized trabecular meshwork (TM) cell lines overexpressing either a control vector or a wild type (WT) or a constitutively active (CA) αvβ3 integrin. Compared to control cells, hierarchical clustering, PANTHER pathway and protein-protein interaction (PPI) analysis of cells overexpressing WT-αvβ3 integrin or CA-αvβ3 integrin resulted in a significant differential expression of genes encoding for transcription factors, adhesion and cytoskeleton proteins, extracellular matrix (ECM) proteins, cytokines and GTPases. Cells overexpressing a CA-αvβ3 integrin also demonstrated an enrichment for genes encoding proteins found in TGFβ2, Wnt and cadherin signaling pathways all of which have been implicated in POAG pathogenesis. These changes were not observed in cells overexpressing WT-αvβ3 integrin. Our results suggest that activation of αvβ3 integrin signaling in TM cells could have significant impacts on TM function and POAG pathogenesis.

摘要

我们实验室的研究表明，αvβ3 整合素介导的信号激活可能导致原发性开角型青光眼 (POAG) 和糖皮质激素诱导性青光眼观察到的纤维样变化。为了确定 αvβ3 整合素信号如何参与这一过程，使用 RNA-Seq 分析来分析过表达对照载体或野生型 (WT) 或组成型激活 (CA) αvβ3 整合素的永生化小梁网 (TM) 细胞系的转录组。与对照细胞相比，过表达 WT-αvβ3 整合素或 CA-αvβ3 整合素的细胞的层次聚类、PANTHER 途径和蛋白质-蛋白质相互作用 (PPI) 分析导致编码转录因子、黏附蛋白和细胞骨架蛋白、细胞外基质 (ECM) 蛋白、细胞因子和 GTPase 的基因的显著差异表达。过表达 CA-αvβ3 整合素的细胞还表现出富含编码 TGFβ2、Wnt 和钙粘蛋白信号通路中发现的蛋白的基因，所有这些都与 POAG 的发病机制有关。在过表达 WT-αvβ3 整合素的细胞中未观察到这些变化。我们的结果表明，TM 细胞中 αvβ3 整合素信号的激活可能对 TM 功能和 POAG 的发病机制有重大影响。

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