LncRNA GTF3C1 promotes diabetic corneal wound healing by regulating GABARAP and PTEN to augment autophagy.

IF 4 1区医学 Q1 OPHTHALMOLOGY

Eye and Vision Pub Date : 2025-08-11 DOI:10.1186/s40662-025-00448-y

Danling Liao, Wenqu Chen, Yuyang Deng, Shijia Wei, Li Wang, Jianzhang Hu

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Abstract

Background: Diabetic keratopathy (DK) is a common ocular complication of diabetes, with its progression closely linked to autophagy regulation. This study aims to explore the role of long non-coding RNAs (lncRNAs) in modulating autophagy during diabetic pathogenesis, focusing on lncRNA general transcription factor IIIC subunit 1 (GTF3C1) and its potential as a therapeutic target for diabetic corneal neuropathy (DCN).

Methods: High-throughput sequencing identified dysregulated lncRNAs in the trigeminal ganglia of diabetic mice. Functional validation included mechanistic studies on lncRNA GTF3C1, miR-542-3p, and autophagy-related targets. Autophagy activity, corneal nerve density, and epithelial healing were quantified using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and histology in diabetic models.

Results: lncRNA GTF3C1 was significantly downregulated in diabetic trigeminal ganglion (TG). It functioned as a molecular sponge for miR-542-3p, alleviating its repression on GABA type A receptor-associated protein (GABARAP) and phosphatase and tensin homolog (PTEN), thereby enhancing autophagy activity. This process promoted corneal nerve fiber regeneration and epithelial wound healing in diabetic mice.

Conclusions: Our findings highlight lncRNA GTF3C1 as a critical regulator of autophagy in diabetic corneal nerves, offering a potential diagnostic and therapeutic target for DCN. This study provides molecular insights into the pathogenesis of DCN and lays the groundwork for future clinical strategies.

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LncRNA GTF3C1通过调节GABARAP和PTEN增强自噬，促进糖尿病角膜创面愈合。

背景：糖尿病性角膜病变（DK）是糖尿病常见的眼部并发症，其进展与自噬调节密切相关。本研究旨在探讨长链非编码rna （lncRNAs）在糖尿病发病过程中调节自噬的作用，重点研究lncRNA一般转录因子IIIC亚基1 （GTF3C1）及其作为糖尿病角膜神经病变（DCN）治疗靶点的潜力。方法：高通量测序鉴定糖尿病小鼠三叉神经节中失调的lncrna。功能验证包括对lncRNA GTF3C1、miR-542-3p和自噬相关靶点的机制研究。采用定量实时聚合酶链反应（qRT-PCR）、免疫荧光和组织学方法对糖尿病模型的自噬活性、角膜神经密度和上皮愈合进行量化。结果：lncRNA GTF3C1在糖尿病三叉神经节（TG）中显著下调。它作为miR-542-3p的分子海绵，减轻其对GABA型a受体相关蛋白（GABARAP）和磷酸酶及紧张素同源物（PTEN）的抑制，从而增强自噬活性。这一过程促进了糖尿病小鼠角膜神经纤维的再生和上皮伤口愈合。结论：我们的研究结果强调lncRNA GTF3C1是糖尿病角膜神经自噬的关键调节因子，为DCN提供了潜在的诊断和治疗靶点。这项研究为DCN的发病机制提供了分子视角，并为未来的临床策略奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Eye and Vision OPHTHALMOLOGY-

CiteScore

8.60

自引率

2.40%

发文量

审稿时长

15 weeks

期刊介绍： Eye and Vision is an open access, peer-reviewed journal for ophthalmologists and visual science specialists. It welcomes research articles, reviews, methodologies, commentaries, case reports, perspectives and short reports encompassing all aspects of eye and vision. Topics of interest include but are not limited to: current developments of theoretical, experimental and clinical investigations in ophthalmology, optometry and vision science which focus on novel and high-impact findings on central issues pertaining to biology, pathophysiology and etiology of eye diseases as well as advances in diagnostic techniques, surgical treatment, instrument updates, the latest drug findings, results of clinical trials and research findings. It aims to provide ophthalmologists and visual science specialists with the latest developments in theoretical, experimental and clinical investigations in eye and vision.