Lysosomal Membrane Protein SCARB2 Mediates the Pathogenesis of Diabetic Retinopathy Through the MAPK/ERK/MMP9 Signaling Pathway.

Authors

Jiawei Fan, Weiqian Cao, Jianghui Wang, Yue Hao, Fangpu Zhang, Yulin Tao, Xiang Gao, Zhengxuan Jiang

Published in

FASEB journal : official publication of the Federation of American Societies for Experimental Biology. Volume 40. Issue 16. Pages e72215. Aug 31, 2026.

Abstract

Diabetic retinopathy (DR), the most prevalent complication of diabetes, remains a major cause of preventable blindness in the working-age population. Retinal microvascular endothelial cell dysfunction is central to DR pathogenesis, and lysosomal pathways play a key role in regulating endothelial injury. This study aims to identify potential core regulators of endothelial dysfunction in DR and explore their regulatory mechanisms, thereby providing therapeutic targets for DR treatment. Transcriptome sequencing was first performed to screen for potential core regulators associated with endothelial dysfunction in DR. Scavenger receptor class B member 2 (SCARB2) was identified as a candidate. Two experimental models were constructed for validation: a HG-stimulated retinal microvascular endothelial cell model and a STZ-induced diabetic rat model. Western blot, tube formation assay, Transwell, EdU proliferation assay, immunofluorescence, and Evans Blue assay were conducted to evaluate the effect of SCARB2 on endothelial dysfunction. RNA-seq analysis was further used to explore the downstream signaling pathway of SCARB2. Transcriptome sequencing confirmed SCARB2 as a potential core regulator of endothelial dysfunction in DR. Under high-glucose conditions, elevated SCARB2 exacerbates retinal microvascular endothelial cell injury and promotes neovascularization and DR progression by upregulating VEGFR1 and VEGFA. Mechanistically, SCARB2 modulates MMP9 via the MAPK/ERK pathway, mediates endothelial cell migration and invasion, and facilitates pathological neovascularization. SCARB2 is a key regulator in the progression of diabetic retinopathy, which modulates endothelial dysfunction by regulating the MAPK/ERK/MMP9 signaling pathway. This study identifies SCARB2 as a novel potential therapeutic target for the treatment of diabetic retinopathy.

PMID:
42634924
Bibliographic data and abstract were imported from PubMed on 24 Aug 2026.

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