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The exosome-transmitted lncRNA LOC100132249 induces endothelial dysfunction in diabetic retinopathy

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posted on 2023-06-22, 17:00 authored by Zizhong Hu, Jingfan Wang, Ting Pan, Xinsheng Li, Chao Tao, Yan Wu, Xingxing Wang, Zhengyu Zhang, Yu Liu, Weiwei Zhang, Changlin Xu, Xinjing Wu, Qinyuan Gu, Yuanyuan Fan, Huiming Qian, Aime Mugisha, Songtao Yuan, Qinghuai Liu, Ping Xie

Diabetic retinopathy (DR), one of the most common microangiopathic complications in diabetes mellitus, causes severe visual damage among working-age populations. Retinal vascular endothelial cells, the key cell type in DR pathogenesis, are responsible for abnormal retinal angiogenesis in advanced stages of DR. The roles of exosomes in DR have been largely unknown. In this study, we report the first evidence that exosomes derived from the vitreous humor of patients with proliferative diabetic retinopathy (PDR-exo) promote proliferation, migration and tube formation of human retinal vascular endothelial cells (HRVECs). We identified lncRNA LOC100132249 enrichment in PDR-exo via high-throughput sequencing. This lncRNA, also mainly derived from HRVECs, promoted angiogenesis both in vitro and in vivo. Mechanistically, LOC100132249 acted as a competing endogenous sponge of microRNA-199a-5p (miR-199a-5p), thus regulating the endothelial-mesenchymal transition (EndMT) promoter SNAI1 via activation of the Wnt/β-catenin pathway, and ultimately resulting in endothelial dysfunction. In conclusion, our findings underscored the pathogenic role of endothelial-derived exosomes via the LOC100132249/miR-199a-5p/SNAI1 axis in DR angiogenesis, and may shed light on new therapeutic strategies for future treatment of DR.

Funding

This work was supported by the National Natural Science Foundation of China (8207097 to P.X., 81970821 to Q.L., 81900875 to Z.H., 12027808 to T.C.), Natural Science Foundation of Jiangsu Province (BK20191059 to Z.H.), Social Development Program of Jiangsu Province (BE2021744 to P.X.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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