Systematically Displaying the Pathogenesis of Keratoconus via Multi-Level Related Gene Enrichment-Based Review

Frontiers in Medicine

Medicine

Wen-Hua Xu¹  Ying Liu²  Zhi-Xia Zhou²  Kun Wang²  Xiao-Dan Hao²  Chan Shan²  Pei-Feng Li²  Hua Gao³ 

[1] Department of Inspection, The Medical Faculty of Qingdao University, Qingdao, China;Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China;State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, China;Shandong Eye Hospital, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China;

关键词: keratoconus;    candidate genes;    multi-level combined analysis;    gene enrichment;    pathogenesis;   

DOI  :  10.3389/fmed.2021.770138

 received in 2021-09-03, accepted in 2021-12-31,  发布年份 2022

来源: Frontiers

【 摘 要 】

Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the reported genes involved in KC, and performed an enrichment analysis of genes identified at the genome, transcription, and protein levels respectively. Combined analysis of multi-level results revealed their shared genes, gene ontology (GO), and pathway terms, to explore the possible pathogenesis of KC. After an initial search, 80 candidate genes, 2,933 transcriptional differential genes, and 947 differential proteins were collected. The candidate genes were significantly enriched in extracellular matrix (ECM) related terms, Wnt signaling pathway and cytokine activities. The enriched GO/pathway terms of transcription and protein levels highlight the importance of ECM, cell adhesion, and inflammatory once again. Combined analysis of multi-levels identified 13 genes, 43 GOs, and 12 pathways. The pathogenic relationships among these overlapping factors maybe as follows. The gene mutations/variants caused insufficient protein dosage or abnormal function, together with environmental stimulation, leading to the related functions and pathways changes in the corneal cells. These included response to the glucocorticoid and reactive oxygen species; regulation of various signaling (P13K-AKT, MAPK and NF-kappaB), apoptosis and aging; upregulation of cytokines and collagen-related enzymes; and downregulation of collagen and other ECM-related proteins. These undoubtedly lead to a reduction of extracellular components and induction of cell apoptosis, resulting in the loosening and thinning of corneal tissue structure. This study, in addition to providing information about the genes involved, also provides an integrated insight into the gene-based etiology and pathogenesis of KC.

【 授权许可】

Unknown   
Copyright © 2022 Hao, Gao, Xu, Shan, Liu, Zhou, Wang and Li.