Dataset Information

Corin Is Downregulated in Renal Ischemia/Reperfusion Injury and Is Associated with Delayed Graft Function after Kidney Transplantation.

ABSTRACT: Renal ischemia/reperfusion (IR) injury is one of the most important risk factors for the occurrence of delayed graft function (DGF) after kidney transplantation; however, its mechanism remains not fully understood. In the present study, we screened differentially expressed genes in a murine model of renal IR injury by using high-throughput assays. We identified Corin as one of the most significantly downregulated genes among 2218 differentially expressed genes (?2-fold, P < 0.05). By using a real-time qPCR assay, we observed that the expression of renal Corin in IR-injured mice was reduced to 11.5% of the sham-operated mice and that the protein level of renal Corin in IR-injured mice was also downregulated. Interestingly, renal IR injury in mice induced the downregulation of Corin in heart tissues, suggesting that the overall synthesis of Corin may be suppressed. We recruited 11 recipients complicated with DGF and 16 without DGF, and plasma Corin concentrations were determined by ELISA. We observed that the plasma Corin levels were indeed reduced in recipients complicated with DGF (0.98 vs. 1.95?ng/ml, P < 0.05). These findings demonstrate that Corin may be a potential biomarker of DGF after kidney transplantation and may participate in the regulation of renal IR injury.

SUBMITTER: Hu X

PROVIDER: S-EPMC6350528 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Corin Is Downregulated in Renal Ischemia/Reperfusion Injury and Is Associated with Delayed Graft Function after Kidney Transplantation.

Hu Xinyi X Su Ming M Lin Jun J Zhang Lei L Sun Wen W Zhang Jian J Tian Ye Y Qiu Wei W

Disease markers 20190114

Renal ischemia/reperfusion (IR) injury is one of the most important risk factors for the occurrence of delayed graft function (DGF) after kidney transplantation; however, its mechanism remains not fully understood. In the present study, we screened differentially expressed genes in a murine model of renal IR injury by using high-throughput assays. We identified <i>Corin</i> as one of the most significantly downregulated genes among 2218 differentially expressed genes (≥2-fold, <i>P</i> < 0.05). ...[more]

PMID: 30766618

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Project description:BackgroundIschemia reperfusion injury (IRI) is an inevitable process in renal transplantation, which is closely related to serious postoperative complications such as delayed graft function (DGF), acute rejection and graft failure. Neutrophil extracellular traps (NETs) are extracellular DNA structures decorated with various protein substances released by neutrophils under strong signal stimulation. Recently, NETs have been found to play an important role in the process of IRI. This study aimed to comprehensively analyze the expression landscape of NET-related genes (NRGs) during IRI, identify clusters with different degrees of IRI and construct robust DGF and long-term graft survival predictive strategies.MethodsThe microarray and RNA-seq datasets were obtained from the GEO database. Differentially expressed NRGs (DE-NRGs) were identified by the differential expression analysis, and the NMF algorithm was used to conduct a cluster analysis of IRI samples. Machine learning algorithms were performed to screen DGF-related hub NRGs, and DGF and long-term graft survival predictive strategies were constructed based on these hub NRGs. Finally, we verified the expression of Cxcl1 and its effect on IRI and NETs generation in the mouse IRI model.ResultsThis study revealed two IRI clusters (C1 and C2 clusters) with different molecular features and clinical characteristics. Cluster C1 was characterized by active metabolism, mild inflammation and lower incidence of DGF, while Cluster C2 was inflammation activated subtype with a higher incidence of DGF. Besides, based on DGF-related hub NRGs, we successfully constructed robust DGF and long-term graft survival predictive strategies. The mouse renal IRI model verified that Cxcl1 was significantly upregulated in renal tissues after IRI, and using a CXCL8/CXCL1 inhibitor could significantly improve renal function, alleviate renal tubular necrosis, tissue inflammatory response, and NET formation.ConclusionThis study identified two distinct IRI clusters based on DE-NRGs and constructed robust prediction methods for DGF and graft survival, which can provide references for early prevention and individualized treatment of various postoperative complications after renal transplantation.

Dataset Information

Corin Is Downregulated in Renal Ischemia/Reperfusion Injury and Is Associated with Delayed Graft Function after Kidney Transplantation.

Publications

Corin Is Downregulated in Renal Ischemia/Reperfusion Injury and Is Associated with Delayed Graft Function after Kidney Transplantation.

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