Dataset Information

Proteomic analysis of aqueous humor and rejected graft in pig-to-nonhuman primate corneal xenotransplantation

ABSTRACT: Although pig-to-nonhuman primate (NHP) corneal xenotransplantation has shown long-term graft survival, xenogeneic antigenrelated immune responses are still stronger than allogenic antigen-associated responses. Therefore, there is an unmet need to investigate major rejection pathways in corneal xenotransplantation, even with immunosuppression. This study aimed to identify biomarkers in aqueous humor for predicting rejection and to investigate rejection-related pathways in grafts from NHPs transplanted with porcine corneas following administration of steroids combined with tacrolimus/rituximab. NHPs who had received corneas from wild‐type (WT) or α‐1,3‐galactosyltransferase gene‐knockout (GTKO) pigs were divided into groups with or without rejection according to clinical examinations. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the proteomes of corneal tissues or aqueous humor. The biological functions of differentially expressed proteins (DEPs) were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathways and protein–protein interaction network analysis. Among the 66 DEPs in aqueous humor, complement proteins (C3, C5, and C9) and cholesterol metabolic proteins (APOA1 and APOA2) were related to xenogeneic rejection as biomarkers, and alternative pathways of the complement system seemed to be important in xenogeneic graft rejection. Among 416 DEPs of the cornea, NF‐κB1 and proteosomes (PSMD7, PSMA5, and PSMD3) seemed to be related with xenogeneic graft rejection. Additionally, oxidative phosphorylation and leukocyte activation‐related pathways are involved in rejection. Overall, our proteomic approach highlights the important role of NF‐κB1, proteosomes, oxidative phosphorylation, and leukocyte activation-related inflammation in the cornea, and the relevance of complement pathways of the aqueous humor as a predictive biomarker of xenogeneic rejection.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Macaca Mulatta (rhesus Macaque) Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Cornea

SUBMITTER: Jaewon Oh

LAB HEAD: Jae Won Oh

PROVIDER: PXD031320 | Pride | 2022-05-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20190125_Transplanted_AH_Rejected_GTKO_R21.raw	Raw
	20190125_Transplanted_AH_Rejected_GTKO_R701.raw	Raw
	20190125_Transplanted_AH_Rejected_GTKO_R702.raw	Raw
	20190125_Transplanted_AH_Rejected_Wild_NR_R11.raw	Raw
	20190125_Transplanted_AH_Rejected_Wild_NR_R114.raw	Raw

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Publications

Proteomics Analysis of Aqueous Humor and Rejected Graft in Pig-to-Non-Human Primate Corneal Xenotransplantation.

Oh Jae Won JW Yoon Chang Ho CH Ryu Jin Suk JS Kim Kwang Pyo KP Kim Mee Kum MK

Frontiers in immunology 20220324

Although pig-to-non-human primate (NHP) corneal xenotransplantation has shown long-term graft survival, xenogeneic antigen-related immune responses are still stronger than allogeneic antigen-associated responses. Therefore, there is an unmet need to investigate major rejection pathways in corneal xenotransplantation, even with immunosuppression. This study aimed to identify biomarkers in aqueous humor for predicting rejection and to investigate rejection-related pathways in grafts from NHPs tran ...[more]

PMID: 35401527

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