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Renoprotective Mechanism of Remote Ischemic Preconditioning Based on Transcriptomic Analysis in a Porcine Renal Ischemia Reperfusion Injury Model

 Young Eun Yoon  ;  Kyung Hwa Choi  ;  Sook Young Kim  ;  Young In Cho  ;  Kwang Suk Lee  ;  Kwang Hyun Kim  ;  Seung Choul Yang  ;  Woong Kyu Han 
 PLOS ONE, Vol.10(10) : e0141099, 2015 
Journal Title
Issue Date
Animals ; Cytokines/genetics ; Extracellular Signal-Regulated MAP Kinases/genetics ; Female ; Gene Expression Profiling/methods ; Ischemic Preconditioning/methods ; Kidney/injuries* ; Kidney/metabolism* ; Nephrectomy/methods ; Receptors, Cytokine/genetics ; Reperfusion Injury/genetics* ; Swine ; Warm Ischemia/methods
Ischemic preconditioning (IPC) is a well-known phenomenon in which tissues are exposed to a brief period of ischemia prior to a longer ischemic event. This technique produces tissue tolerance to ischemia reperfusion injury (IRI). Currently, IPC's mechanism of action is poorly understood. Using a porcine single kidney model, we performed remote IPC with renal IRI and evaluated the IPC mechanism of action. Following left nephrectomy, 15 female Yorkshire pigs were divided into three groups: no IPC and 90 minutes of warm ischemia (control), remote IPC immediately followed by 90 minutes of warm ischemia (rIPCe), and remote IPC with 90 minutes of warm ischemia performed 24 hours later (rIPCl). Differential gene expression analysis was performed using a porcine-specific microarray. The microarray analysis of porcine renal tissues identified 1,053 differentially expressed probes in preconditioned pigs. Among these, 179 genes had altered expression in both the rIPCe and rIPCl groups. The genes were largely related to oxidation reduction, apoptosis, and inflammatory response. In the rIPCl group, an additional 848 genes had altered expression levels. These genes were primarily related to immune response and inflammation, including those coding for cytokines and cytokine receptors and those that play roles in the complement system and coagulation cascade. In the complement system, the membrane attack complex was determined to be sublytic, because it colocalized with phosphorylated extracellular signal-regulated kinase. Furthermore, alpha 2 macroglobulin, tissue plasminogen activator, uterine plasmin trypsin inhibitor, and arginase-1 mRNA levels were elevated in the rIPCl group. These findings indicate that remote IPC produces renoprotective effects through multiple mechanisms, and these effects develop over a long timeframe rather than immediately following IPC.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kwang Hyun(김광현)
Yang, Seung Choul(양승철)
Yoon, Young Eun(윤영은)
Lee, Kwang Suk(이광석) ORCID logo https://orcid.org/0000-0002-7961-8393
Cho, Young In(조영인)
Choi, Kyung Hwa(최경화)
Han, Woong Kyu(한웅규) ORCID logo https://orcid.org/0000-0002-2527-4046
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