lncRNA TGFβ2-AS1 promotes ECM production via TGF-β2 in human trabecular meshwork cells

Abstract

Evidence indicates that long noncoding RNAs (lncRNAs) participate in the regulation of various physiological and pathological processes including organ fibrosis and eye-related diseases. The important pathological manifestations of open-angle glaucoma (OAG) are human trabecular meshwork cells (HTMCs) apoptosis and excessive deposition of extracellular matrix (ECM) components in TM, which can cause pathological changes in the outflow pathway. To investigate the role and regulation mechanism of lncRNA in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (H₂O₂) followed by RNA sequencing and found that subsets of lncRNAs and mRNAs that closely associate with TGF-β signaling are differentially regulated in these cells. We then constructed a network with the TGF-β2 -colocalized and -coexpressed lncRNAs, to investigate the effects and regulatory mechanisms of the potential lncRNAs on ECM deposition in HTMCs. The gain-of-function and loss-of-function experiments demonstrated that lnc-TGFβ2-AS1 promotes ECM production via TGF-β2 in HTMC, suggesting that lnc-TGFβ2-AS1 may be a potential glaucoma treatment target.

Keywords: Glaucoma; Oxidative stress; TGF-β2; Trabecular meshwork cells; lncRNA.