VR-10 polypeptide interacts with CD36 to induce cell apoptosis and autophagy in choroid-retinal endothelial cells: Identification of VR-10 as putative novel therapeutic agent for choroid neovascularization (CNV) treatment

• DOI: 10.1016/j.peptides.2022.170868
• Publication Date: 2022-09-05T21:56:44Z
• Authors: Run Tian; Aiping Deng; Xiaocong Pang; Yunli Chen; Yufei Gao; Hai Liu; Zhulin Hu
• Keywords: PEDF

Choroid neovascularization (CNV) is important adverse pathological changes that contributes to the aggravation of hypoxic-ischemic eye diseases, and our preliminary work evidences thrombospondin-1 (TSP-1) synthetic polypeptide VR-10 may be candidate therapeutic agent for treatment CNV, but its detailed effects molecular mechanisms are not fully delineated. In this study, CNV models in BN rats were established by using laser photocoagulation method, which further subjected peptide treatment. The RNA-seq bioinformatics analysis suggested significantly altered expression patterns genes rat ocular tissues, changed especially enriched CD36-associated signal pathways. Next, performing Real-Time qPCR Western Blot analysis, we expectedly found upregulated anti-angiogenesis biomarker (PEDF) downregulated pro-angiogenesis biomarkers (VEGF, HIF-1 IL-17) tissues. addition, evidenced CDK2, CDK4, CDK6, Cyclin D1 D2 induce cell cycle arrest, cleaved Caspase-3, Bax Bcl-2 promote apoptosis, increased LC3B-II/I ratio facilitate p62 degradation autophagy RF/6A cells, all reversed knocking down CD36. Moreover, PEDF, decreased levels VEGF, IL-17 block angiogenesis cells a CD36-dependent manner. Taken together, interacts with receptor CD36 regulate biological functions these data suggest putative drug clinic.