Tianjin Eye Hospital & Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Nankai University, Tianjin 300020, China.
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China.
Oxid Med Cell Longev. 2020 Nov 24;2020:4692034. doi: 10.1155/2020/4692034. eCollection 2020.
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.
原发性开角型青光眼（POAG）是一种导致不可逆视力丧失的主要原因，在全球范围内其患病率不断上升，且临床严重程度更高。越来越多的证据表明，非编码 RNA（ncRNA）参与了纤维化过程，这被认为是 POAG 的主要原因。在这里，我们在氧化应激下筛选出一种在人眼小梁细胞（HTMCs）中差异表达的环状 RNA（命名为 circHBEGF），它是从 pre-HBEGF 剪接而来的。circHBEGF 促进细胞外基质（ECM）基因（纤连蛋白和胶原 I）的表达。进一步的研究表明，circHBEGF 可以作为 miRNA 海绵与 miR-646 竞争结合，从而调节 HTMCs 中的 EGFR 表达。重要的是，HBEGF 还可以激活 EGF 信号通路，通过该通路可以在 HTMCs 中转录激活 ECM 基因。总之，本研究通过 miR646/EGFR 通路探讨了氧化应激诱导的 circHBEGF 在调节 HTMCs 中 ECM 产生中的功能和分子机制。这些发现进一步阐明了发病机制，并可能为 POAG 的分子治疗确定新的靶点。
