Dataset Information

Oxidative Stress-Induced circHBEGF Promotes Extracellular Matrix Production via Regulating miR-646/EGFR in Human Trabecular Meshwork Cells.

ABSTRACT: Primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss, presents with increased prevalence and a higher degree of clinical severity in the world. Growing evidence has shown that ncRNAs are involved in the fibrotic process, which is thought to be the proegumenal cause of POAG. Here, we screened out a differentially expressed circRNA (named circHBEGF) in human trabecular meshwork cells (HTMCs) under oxidative stress, which is spliced from pre-HBEGF. circHBEGF promotes the expression of extracellular matrix (ECM) genes (fibronectin and collagen I). Further studies revealed that circHBEGF could competitively bind to miR-646 as a miRNA sponge to regulate EGFR expression in HTMCs. Importantly, HBEGF can also activate EGF signaling pathways, through which can transcriptionally activate ECM genes in HTMCs. In summary, this study investigates the functions and molecular mechanisms of oxidative stress-induced circHBEGF in the regulation of ECM production in HTMCs through the miR646/EGFR pathway. These findings further elucidate the pathogenic mechanism and may identify novel targets for the molecular therapy of POAG.

SUBMITTER: Shen W

PROVIDER: S-EPMC7722639 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Oxidative Stress-Induced circHBEGF Promotes Extracellular Matrix Production via Regulating miR-646/EGFR in Human Trabecular Meshwork Cells.

Shen Wencui W Wang Chengzhi C Huang Bingqing B

Oxidative medicine and cellular longevity 20201124

Primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss, presents with increased prevalence and a higher degree of clinical severity in the world. Growing evidence has shown that ncRNAs are involved in the fibrotic process, which is thought to be the proegumenal cause of POAG. Here, we screened out a differentially expressed circRNA (named circHBEGF) in human trabecular meshwork cells (HTMCs) under oxidative stress, which is spliced from pre-HBEGF. circHBEGF promotes the ...[more]

PMID: 33335643

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Project description:PurposeBiophysical and biochemical attributes of the extracellular matrix are major determinants of cell fate in homeostasis and disease. Ocular hypertension and glaucoma are diseases where the trabecular meshwork tissue responsible for aqueous humor egress becomes stiffer accompanied by changes in its matrisome in a segmental manner with regions of high or low flow. Prior studies demonstrate these alterations in the matrix are dynamic in response to age and pressure changes. The underlying reason for segmentation or differential response to pressure and stiffening are unknown. This is largely due to a lack of appropriate models (in vitro or ex vivo) to study this phenomena.MethodsPrimary trabecular meshwork cells were isolated from segmental flow regions, and cells were cultured for 4 weeks in the presence or absence or dexamethasone to obtain cell derived matrices (CDM). The biomechanical attributes of the CDM, composition of the matrisome, and incidence of crosslinks were determined by atomic force microscopy and mass spectrometry.ResultsData demonstrate that matrix deposited by cells from low flow regions are stiffer and exhibit a greater number of immature and mature crosslinks, and that these are exacerbated in the presence of steroid. We also show a differential response of high or low flow cells to steroid via changes observed in the matrix composition. However, no correlations were observed between elastic moduli and presence or absence of mature and immature crosslinks in the CDMs.ConclusionRegardless of a direct correlation between matrix stiffness and crosslinks, we observed distinct differences in the composition and mechanics of the matrices deposited by segmental flow cells. These results suggest distinct differences in cellular identify and likely a basis for mechanical memory post isolation and culture. Nevertheless, we conclude that although a mechanistic basis for matrix stiffness was undetermined in this study, it is a viable tool to study cell-matrix interactions and further our understanding of trabecular meshwork pathobiology.

Dataset Information

Oxidative Stress-Induced circHBEGF Promotes Extracellular Matrix Production via Regulating miR-646/EGFR in Human Trabecular Meshwork Cells.

Publications

Oxidative Stress-Induced circHBEGF Promotes Extracellular Matrix Production via Regulating miR-646/EGFR in Human Trabecular Meshwork Cells.

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