Blockade of Cysteine-rich Protein 61 Attenuates Renal Inflammation and Fibrosis after Ischemic Kidney Injury.

This study aimed to investigate the role of Cysteine-rich protein 61 (Cyr61) after unilateral kidney ischemia-reperfusion injury (IRI) in mice. After IRI, increased expression of Cyr61 was detected, predominately in the proximal tubular epithelium. This was confirmed by in vitro experiments, which showed that hypoxia stimulates Cyr61 expression in cultured proximal tubular epithelial cells. The proinflammatory property of Cyr61 was indicated by its ability to upregulate monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-6. Additionally, we found elevated urinary Cyr61 excretion in patients with AKI. Notably, treating mice with an anti-Cyr61 antibody attenuated the upregulation of kidney MCP-1, IL-6, IL-1β, macrophage inflammatory protein-2, and reduced the infiltration of F4/80-positive macrophages at day 7 and 14 after IRI. In addition, blocking Cyr61 reduced the mRNA expression of collagen, transforming growth factor-β, and plasminogen activator inhibitor-1, the degree of collagen fibril accumulation, as evaluated by picrosirius red staining, and the levels of α-smooth muscle actin proteins by day 14. Concurrently, in the treated group, peritubular microvascular density was more preserved at day 14. We conclude that Cyr61 blockade inhibits the triad of inflammation, interstitial fibrosis, and capillary rarefaction after severe ischemic AKI. These studies expand the knowledge of the mechanisms underlying the AKI-to-CKD transition and suggest that Cyr61 is a pot...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research