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Integrated Analysis of Transcriptome and Proteome of the Human Cornea and Aqueous Humor Reveal Novel Biomarkers for Corneal Endothelial Cell Dysfunction

Authors
 Chae-Eun Moon  ;  Chang Hwan Kim  ;  Jae Hun Jung  ;  Young Joo Cho  ;  Kee Yong Choi  ;  Kyusun Han  ;  Kyoung Yul Seo  ;  Hyung Keun Lee  ;  Yong Woo Ji 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.24(20) : 15354, 2023-10 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2023-10
MeSH
Angiopoietin-Like Protein 7 ; Angiopoietin-like Proteins / metabolism ; Aqueous Humor* / metabolism ; Biomarkers / metabolism ; Cornea / metabolism ; Endothelial Cells / metabolism ; Humans ; Proteome / metabolism ; Proteomics ; Transcriptome*
Keywords
aqueous humor ; biomarker ; corneal endothelial cell dysfunction ; proteomics ; transcriptomics
Abstract
Earlier studies have reported that elevated protein levels in the aqueous humor (AH) are associated with corneal endothelial cell dysfunction (CECD), but the details of the underlying mechanism as well as specific biomarkers for CECD remain elusive. In the present study, we aimed to identify protein markers in AH directly associated with changes to corneal endothelial cells (CECs), as AH can be easily obtained for analysis. We carried out an in-depth proteomic analysis of patient-derived AH as well as transcriptomic analysis of CECs from the same patients with bullous keratopathy (BK) resulting from CECD. We first determined differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) from CECs and AH in CECD, respectively. By combining transcriptomic and proteomic analyses, 13 shared upregulated markers and 22 shared downregulated markers were observed between DEGs and DEPs. Among these 35 candidates from biomarker profiling, three upregulated markers were finally verified via data-independent acquisition (DIA) proteomic analysis using additional individual AH samples, namely metallopeptidase inhibitor 1 (TIMP1), Fc fragment of IgG binding protein (FCGBP), and angiopoietin-related protein 7 (ANGPTL7). Furthermore, we confirmed these AH biomarkers for CECD using individual immunoassay validation. Conclusively, our findings may provide valuable insights into the disease process and identify biofluid markers for the assessment of CEC function during BK development.
Files in This Item:
T202306134.pdf Download
DOI
10.3390/ijms242015354
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Hwan(김창환)
Seo, Kyoung Yul(서경률) ORCID logo https://orcid.org/0000-0002-9855-1980
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
Ji, Yong Woo(지용우) ORCID logo https://orcid.org/0000-0002-7211-6278
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196725
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