Genome-wide transcriptome profiling of human trabecular meshwork cells treated with TGF-β2

Callaghan, Breedge, Lester, Karen, Lane, Brian, Fan, Xiaochen, Goljanek-Whysall, Katarzyna ORCID: 0000-0001-8166-8800, Simpson, David A, Sheridan, Carl ORCID: 0000-0003-0100-9587 and Willoughby, Colin E (2022) Genome-wide transcriptome profiling of human trabecular meshwork cells treated with TGF-β2 Scientific Reports, 12 (1). 9564-. ISSN 2045-2322, 2045-2322

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Abstract

AbstractGlaucoma is a complex neurodegenerative disease resulting in progressive optic neuropathy and is a leading cause of irreversible blindness worldwide. Primary open angle glaucoma (POAG) is the predominant form affecting 65.5 million people globally. Despite the prevalence of POAG and the identification of over 120 glaucoma related genetic loci, the underlaying molecular mechanisms are still poorly understood. The transforming growth factor beta (TGF-β) signalling pathway is implicated in the molecular pathology of POAG. To gain a better understanding of the role TGF-β2 plays in the glaucomatous changes to the molecular pathology in the trabecular meshwork, we employed RNA-Seq to delineate the TGF-β2 induced changes in the transcriptome of normal primary human trabecular meshwork cells (HTM). We identified a significant number of differentially expressed genes and associated pathways that contribute to the pathogenesis of POAG. The differentially expressed genes were predominantly enriched in ECM regulation, TGF-β signalling, proliferation/apoptosis, inflammation/wound healing, MAPK signalling, oxidative stress and RHO signalling. Canonical pathway analysis confirmed the enrichment of RhoA signalling, inflammatory-related processes, ECM and cytoskeletal organisation in HTM cells in response to TGF-β2. We also identified novel genes and pathways that were affected after TGF-β2 treatment in the HTM, suggesting additional pathways are activated, including Nrf2, PI3K-Akt, MAPK and HIPPO signalling pathways. The identification and characterisation of TGF-β2 dependent differentially expressed genes and pathways in HTM cells is essential to understand the patho-physiology of glaucoma and to develop new therapeutic agents.

Item Type:	Article
Uncontrolled Keywords:	Trabecular Meshwork, Cells, Cultured, Humans, Neurodegenerative Diseases, Glaucoma, Glaucoma, Open-Angle, Gene Expression Profiling, Transforming Growth Factor beta2, Phosphatidylinositol 3-Kinases
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	22 Jun 2022 09:22
Last Modified:	16 Jun 2026 12:08
DOI:	10.1038/s41598-022-13573-8
Open Access URL:	https://www.nature.com/articles/s41598-022-13573-8
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3156967
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