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Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes

Keratoconus (KTCN), characterized by the steeper curvature of the cornea and the thinner central corneal thickness, was a degenerative corneal ectasia with ambiguous etiology and mechanism. We aim to reveal underlying pathological mechanisms of KTCN by multi-level transcriptomic, integrative omics a...

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Autores principales: Sun, Xiao, Zhang, Hao, Shan, Mengyuan, Dong, Yi, Zhang, Lin, Chen, Luxia, Wang, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8914074/
https://www.ncbi.nlm.nih.gov/pubmed/35281826
http://dx.doi.org/10.3389/fgene.2022.782709
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author Sun, Xiao
Zhang, Hao
Shan, Mengyuan
Dong, Yi
Zhang, Lin
Chen, Luxia
Wang, Yan
author_facet Sun, Xiao
Zhang, Hao
Shan, Mengyuan
Dong, Yi
Zhang, Lin
Chen, Luxia
Wang, Yan
author_sort Sun, Xiao
collection PubMed
description Keratoconus (KTCN), characterized by the steeper curvature of the cornea and the thinner central corneal thickness, was a degenerative corneal ectasia with ambiguous etiology and mechanism. We aim to reveal underlying pathological mechanisms of KTCN by multi-level transcriptomic, integrative omics analyses. We performed RNA-sequencing on corneal epithelial samples from seven patients and seven control donors, as well as peripheral matched blood samples from three of the patients and three control donors. After RNA extraction, library construction, and sequencing, differentially expressed genes and splicing events were identified, followed by over-representation analysis. In total, 547 differential expressed genes were identified in KTCN corneal epithelial samples, which were mainly enriched in immune responses and inflammatory processes. WGCNA module analysis, the transcriptomic analysis of peripheral blood samples, multiple omics data, and the meta-analysis of GEO samples confirmed the involvement of immune and inflammatory factors. Besides, 190 and 1,163 aberrant splicing events were identified by rMATS combined with CASH methods in corneal epithelial and blood samples with KCTN. In conclusion, this comprehensive transcriptome analysis of KTCN patients based on patients’ tissue and blood samples uncovered a significant association between immune-inflammatory genes and pathways with KCTN, highlighting the contribution of the perturbed immune signaling to the pathogenesis of KCTN. Our study suggested the importance of measures to control inflammation in the treatment of KCTN.
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spelling pubmed-89140742022-03-12 Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes Sun, Xiao Zhang, Hao Shan, Mengyuan Dong, Yi Zhang, Lin Chen, Luxia Wang, Yan Front Genet Genetics Keratoconus (KTCN), characterized by the steeper curvature of the cornea and the thinner central corneal thickness, was a degenerative corneal ectasia with ambiguous etiology and mechanism. We aim to reveal underlying pathological mechanisms of KTCN by multi-level transcriptomic, integrative omics analyses. We performed RNA-sequencing on corneal epithelial samples from seven patients and seven control donors, as well as peripheral matched blood samples from three of the patients and three control donors. After RNA extraction, library construction, and sequencing, differentially expressed genes and splicing events were identified, followed by over-representation analysis. In total, 547 differential expressed genes were identified in KTCN corneal epithelial samples, which were mainly enriched in immune responses and inflammatory processes. WGCNA module analysis, the transcriptomic analysis of peripheral blood samples, multiple omics data, and the meta-analysis of GEO samples confirmed the involvement of immune and inflammatory factors. Besides, 190 and 1,163 aberrant splicing events were identified by rMATS combined with CASH methods in corneal epithelial and blood samples with KCTN. In conclusion, this comprehensive transcriptome analysis of KTCN patients based on patients’ tissue and blood samples uncovered a significant association between immune-inflammatory genes and pathways with KCTN, highlighting the contribution of the perturbed immune signaling to the pathogenesis of KCTN. Our study suggested the importance of measures to control inflammation in the treatment of KCTN. Frontiers Media S.A. 2022-02-25 /pmc/articles/PMC8914074/ /pubmed/35281826 http://dx.doi.org/10.3389/fgene.2022.782709 Text en Copyright © 2022 Sun, Zhang, Shan, Dong, Zhang, Chen and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Sun, Xiao
Zhang, Hao
Shan, Mengyuan
Dong, Yi
Zhang, Lin
Chen, Luxia
Wang, Yan
Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes
title Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes
title_full Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes
title_fullStr Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes
title_full_unstemmed Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes
title_short Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes
title_sort comprehensive transcriptome analysis of patients with keratoconus highlights the regulation of immune responses and inflammatory processes
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8914074/
https://www.ncbi.nlm.nih.gov/pubmed/35281826
http://dx.doi.org/10.3389/fgene.2022.782709
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