miR-486-5p protects against rat ischemic kidney injury and prevents the transition to chronic kidney disease and vascular dysfunction.

Autor:	Douvris A; Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada., Viñas JL; Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada., Gutsol A; Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada., Zimpelmann J; Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada., Burger D; Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada., Burns KD; Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
Jazyk:	angličtina
Zdroj:	Clinical science (London, England : 1979) [Clin Sci (Lond)] 2024 May 22; Vol. 138 (10), pp. 599-614.
DOI:	10.1042/CS20231752
Abstrakt:	Aim: Acute kidney injury (AKI) increases the risk for progressive chronic kidney disease (CKD). MicroRNA (miR)-486-5p protects against kidney ischemia-reperfusion (IR) injury in mice, although its long-term effects on the vasculature and development of CKD are unknown. We studied whether miR-486-5p would prevent the AKI to CKD transition in rat, and affect vascular function. Methods: Adult male rats were subjected to bilateral kidney IR followed by i.v. injection of liposomal-packaged miR-486-5p (0.5 mg/kg). Kidney function and histologic injury were assessed after 24 h and 10 weeks. Kidney endothelial protein levels were measured by immunoblot and immunofluorescence, and mesenteric artery reactivity was determined by wire myography. Results: In rats with IR, miR-486-5p blocked kidney endothelial cell increases in intercellular adhesion molecule-1 (ICAM-1), reduced neutrophil infiltration and histologic injury, and normalized plasma creatinine (P<0.001). However, miR-486-5p attenuated IR-induced kidney endothelial nitric oxide synthase (eNOS) expression (P<0.05). At 10 weeks, kidneys from rats with IR alone had decreased peritubular capillary density and increased interstitial collagen deposition (P<0.0001), and mesenteric arteries showed impaired endothelium-dependent vasorelaxation (P<0.001). These changes were inhibited by miR-486-5p. Delayed miR-486-5p administration (96 h, 3 weeks after IR) had no impact on kidney fibrosis, capillary density, or endothelial function. Conclusion: In rats, administration of miR-486-5p early after kidney IR prevents injury, and protects against CKD development and systemic endothelial dysfunction. These protective effects are associated with inhibition of endothelial ICAM-1 and occur despite reduction in eNOS. miR-486-5p holds promise for the prevention of ischemic AKI and its complications. (© 2024 The Author(s).)
Databáze:	MEDLINE
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