Abstract
Primary open-angle glaucoma (POAG) can result in irreversible blindness. As an important etiological factor, oxidative stress can elicit extraordinary increase of extracellular matrix (ECM) in trabecular meshwork-schlemm canal, to increase aqueous humor outflow resistance and elevate intraocular pressure. Although autophagy plays an important role in clearing ECM, the functions of long non-coding RNAs (lncRNAs) in autophagy induced by oxidative stress in human trabecular meshwork cells (HTMCs) remain unclear. In our study, oxidative stress induced the expression of ECM and autophagy in TMCs after H2O2 treatment. Meanwhile, a novel lncRNA ENST00000523905 and tumor protein 53-induced nuclear protein 1 (TP53INP1) were elevated in TMCs treated with H2O2. Similar to treatment with 3-MA (an inhibitor of autophagy), knocking-down the expression of TP53INP1 or ENST00000523905 could suppress the autophagy of TMCs induced by H2O2, which increased the level of ECM. Furthermore, the inhibition of ENST00000523905 decreased the expression of TP53INP1. ENST00000523905 could recruit and directly bind with CCAAT/enhancer (C/EBPβ), which can promote the expression of TP53INP1. Taken together, our findings demonstrated that ENST00000523905 may increase autophagy via enhancing TP53INP1 expression through binding with C/EBPβ, resulting in oxidative stress-induced decrease in ECM in HTMCs.
Keywords:
Autophagy; Human trabecular meshwork cells; Long non-coding RNA; Oxidative stress; Tumor protein 53-induced nuclear protein 1.