Overexpression and Activation of αvβ3 Integrin Differentially Affects TGFβ2 Signaling in Human Trabecular Meshwork Cells
Autor: | Kristy Meyer, Donna M. Peters, Mark S. Filla, Jennifer A. Faralli |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
QH301-705.5 Integrin Article Extracellular matrix 03 medical and health sciences 0302 clinical medicine Trabecular Meshwork medicine Humans Biology (General) Transcription factor Cell Line Transformed biology Sequence Analysis RNA Cadherin Chemistry Gene Expression Profiling Wnt signaling pathway General Medicine Integrin alphaVbeta3 Cell biology glaucoma 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Cell culture integrins 030221 ophthalmology & optometry biology.protein sense organs Trabecular meshwork Signal transduction Glaucoma Open-Angle Signal Transduction |
Zdroj: | Cells Cells, Vol 10, Iss 1923, p 1923 (2021) Volume 10 Issue 8 |
ISSN: | 2073-4409 |
Popis: | 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. |
Databáze: | OpenAIRE |
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