AKI - experimental models

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Introduction and Aims: Clinical studies have demonstrated the risk of chronic kidney disease after the occurrence of an acute kidney injury (AKI).Experimental works indicate that AKI result in incomplete repair, persistent tubulointerstitial inflammation and fibrosis.Cysteine-rich protein 61 (Cyr61), a secreted matrix-associated protein, has been found to be up-regulated in the kidney ischemia reperfusion injury (IRI) animal model.The present study aimed to investigate the role of Cyr61 in the kidney after IRI.Methods: Using mouse unilateral IRI model, we analyzed gene and protein expression of Cyr61.We further investigated the effect of blockade of Cyr61 in unilateral IRI mice by treating polyclonal anti-Cyr61 antibody or non-specific IgG.In addition, we used proximal tubular epithelial (NRK-52E) cells for cell culture studies.Results: After IRI, kidney Cyr61 expression increased significantly in both mRNA and protein level.Immunofluorescence staining indicated Cyr61 was predominantly expressed in renal proximal tubular epithelial cells.This was supported by in vitro studies showing hypoxia condition stimulate Cyr61 expression in NRK-52E cells.Dailytreatment with anti-Cyr61 antibody produced a decrease in the renal type 1 collagen, PAI-1, MCP-1, and IL-1 gene expression, as well as α-SMA protein production at day 14 after IRI.The degree of collagen fibril accumulation, evaluated by picrosirius red staining, and macrophage infiltration were both attenuated by the Cyr61 blockade on day 7 and 14.Concurrently, renal VEGF-A gene expression was enhanced and vessel density was more preserved at day 14 in the treatment group.Conclusions: Renal Cyr61 expression by tubular epithelial cells is enhanced after IRI.Our findings suggest that Cyr61 contributes to the renal inflammation, vascular rarefaction, and fibrosis after ischemic AKI.

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