Identification of critical autophagy-related proteins in diabetic retinopathy: A multi-dimensional computational study.

Autor: Sarmah DT; Complex Analysis Group, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India., Gujjar S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India., Mathapati S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India., Bairagi N; Centre for Mathematical Biology and Ecology, Department of Mathematics, Jadavpur University, Kolkata 700032, India., Chatterjee S; Complex Analysis Group, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India. Electronic address: samrat.chatterjee@thsti.res.in.
Jazyk: angličtina
Zdroj: Gene [Gene] 2023 May 25; Vol. 866, pp. 147339. Date of Electronic Publication: 2023 Mar 05.
DOI: 10.1016/j.gene.2023.147339
Abstrakt: Diabetic retinopathy (DR) is a common consequence of diabetes mellitus and a primary cause of visual impairment in middle-aged and elderly individuals. DR is susceptible to cellular degradation facilitated by autophagy. In this study, we have employed a multi-layer relatedness (MLR) approach to uncover novel autophagy-related proteins involved in DR. The objective of MLR is to determine the relatedness of autophagic and DR proteins by incorporating both expression and prior-knowledge-based similarities. We constructed a prior knowledge-based network and identified the topologically significant novel disease-related candidate autophagic proteins (CAPs). Then, we evaluated their significance in a gene co-expression and a differentially-expressed gene (DEG) network. Finally, we investigated the proximity of CAPs to the known disease-related proteins. Leveraging this methodology, we identified three crucial autophagy-related proteins, TP53, HSAP90AA1, and PIK3R1, which can influence the DR interactome in various layers of heterogeneity of clinical manifestations. They are strongly related to multiple detrimental characteristics of DR, such as pericyte loss, angiogenesis, apoptosis, and endothelial cell migration, and hence may be used to prevent or delay the progression and development of DR. We evaluated one of the identified targets, TP53, in a cell-based model and found that its inhibition resulted in reduced angiogenesis in high glucose condition required to control DR.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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