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Soluble receptor for advanced glycation end-products attenuates sepsis-induced acute kidney injury

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dc.contributor.author박선영-
dc.date.accessioned2017-07-07T16:10:47Z-
dc.date.available2017-07-07T16:10:47Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/148871-
dc.description의과대학/박사-
dc.description.abstractBackground Acute kidney injury (AKI), an important complication of sepsis, is considered to be resulted from immune-mediated tubular damage. Receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of numerous inflammatory conditions including sepsis. Meanwhile, soluble RAGE (sRAGE) competitively inhibits the binding of RAGE ligands to RAGE, and thus attenuates the development of RAGE-induced inflammatory cascades. However, little is known about the efficacy of sRAGE in septic AKI (S-AKI). In this study, I investigated the possible therapeutic role of sRAGE in S-AKI models, both in vivo and in vitro. Methods In vivo, C57/BL6 mice were subjected to cecal ligation and puncture (CLP) or sham operation (control), and sacrificed after 24 hr. CLP mice were injected either with diluent or sRAGE intraperitoneally (CLP+sRAGE) 1 hr before operation. In vitro, in addition, NRK-52E cells were incubated with DMEM media with or without lipopolysaccharide (LPS, 1 μg/ml). To examine the effect of RAGE inhibition on LPS-induced tubular cell injury, NRK-52E cells were also treated with sRAGE (1 μg/ml) or RAGE siRNA. Blood urea nitrogen (BUN) and serum creatinine (Cr) levels were determined to evaluate renal function. RAGE-associated signaling molecule and apoptosis-related protein expressions were evaluated by Western blot analysis and immunohistochemistry. Results BUN and serum Cr levels were significantly higher in CLP model compared to control mice, and these increments were significantly abrogated in CLP+sRAGE mice (P < 0.05). Renal MyD88, phospho-ERK, phospho-p-38, and phospho-JNK protein expression in the CLP group were also significantly increased compared to the control group, and these changes were significantly ameliorated by sRAGE treatment in CLP mice. Compared to the control group, moreover, apoptosis-related protein expressions were significantly increased in the kidney of CLP mice, and sRAGE treatment significantly attenuated these increases in the CLP mice kidney. In vitro, HMGB1 and RAGE protein expression were significantly increased in LPS-stimulated NRK-52E cells, and sRAGE significantly abrogated these LPS-induced of HMGB1 and RAGE protein expression. Similarly, RAGE-associated activation of mitogen-activated protein kinase and increase in apoptosis-related protein expression in LPS-stimulated cells were significantly ameliorated by sRAGE. Furthermore, the increase in nuclear translocation of NF-κB and ICAM-1 protein expression by LPS were significantly attenuated by sRAGE in NRK-52E cells. Conclusions These findings suggest that RAGE plays an important role in S-AKI and its inhibition by sRAGE may be a potential therapeutic target for AKI in severe sepsis. Key words: receptor for advanced glycation end products (RAGE), soluble RAGE (sRAGE), sepsis, acute kidney injury (AKI)-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.publisherGraduate School, Yonsei University-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleSoluble receptor for advanced glycation end-products attenuates sepsis-induced acute kidney injury-
dc.title.alternative패혈성 급성 신손상 모델에서 soluble receptor for advanced glycation end–products (sRAGE)의 신보호 효과-
dc.typeThesis-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.localIdA01499-
dc.contributor.alternativeNamePark, Sun Young-
dc.contributor.affiliatedAuthor박선영-
dc.type.localDissertation-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 3. Dissertation

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