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ADAMTS13 protects mice against renal ischemia-reperfusion injury by reducing inflammation and improving endothelial function
Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
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2019 (English)In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 1, p. F134-F145Article in journal (Refereed) Published
Abstract [en]

Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disintegrin and metalloprotease with thrombospondin motifs 13 (rhADAMTS13) provides protection against inflammation. Therefore, we hypothesized that ADAMTS13 might protect against AKI by reducing inflammation. Bilateral renal ischemia-reperfusion injury (I/R) was used as AKI models in this study. Prophylactic infusion of rhADAMTS13 was employed to investigate potential mechanisms of renal protection. Renal function, inflammation, and microvascular endothelial function were assessed after 24 h of reperfusion. Our results showed that I/R mice increased plasma von Willebrand factor levels but decreased ADAMTS13 expression. Administration of rhADAMTS13 to I/R mice recovered renal function, histological injury, and apoptosis. Renal inflammation was reduced by rhADAMTS13, accompanied with the downregulation of p38/extracellular signal-regulated protein kinase phosphorylation and cyclooxygenase-2 expression. rhADAMTS13 restored vasodilation in afferent arterioles in I/R mice. Furthermore, rhADAMTS13 treatment enhanced phosphorylation of Akt at Set(473) and eNOS at Ser(1177). Administration of the Akt pathway inhibitor wortmannin reduced the protective effect of rhADAMTS13. Our conclusions are that treatment with rhADAMTS13 ameliorates renal I/R injury by reducing inflammation, tubular cell apoptosis. and improving microvascular endothelial dysfunction. rhADAMIS13 could be a promising strategy to treat AKI in clinical settings.

Place, publisher, year, edition, pages
2019. Vol. 316, no 1, p. F134-F145
Keywords [en]
acute kidney injury, endothelial dysfunction, ischemia and reperfusion, rhADAMTS13
National Category
Urology and Nephrology Physiology
Identifiers
URN: urn:nbn:se:uu:diva-375849DOI: 10.1152/ajprenal.00405.2018ISI: 000455616200014PubMedID: 30461292OAI: oai:DiVA.org:uu-375849DiVA, id: diva2:1284745
Funder
Swedish Society of MedicineSwedish Heart Lung FoundationGerman Research Foundation (DFG), DFG PA 479/10-1; PA 479/10-2Available from: 2019-02-01 Created: 2019-02-01 Last updated: 2019-02-01Bibliographically approved

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Hultström, Michael

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