Corin protects against acute kidney injury in mice through anti-inflammatory effects.

Corin is a type II transmembrane serine protease mainly expressed in the heart. Recently, corin was detected in the kidney and was reported to be associated with multiple kidney diseases. To date, its effect on acute kidney injury (AKI) has not been clarified. Here, we found that corin was constitutively expressed in renal tubules, especially in proximal and distal tubular epithelial cells. The expression of corin was dramatically reduced in ischemia/reperfusion injury (IRI)-induced AKI mouse model and oxygen-glucose deprivation (OGD)-induced human proximal tubular epithelial (HK-2) cells injury model, suggesting a potential role of corin in AKI. Corin deficient mice exhibited aggravated renal injury in AKI, as indicated by higher elevation of serum creatinine (SCr) and blood urea nitrogen (BUN), more severe tubular damage, and increased cell death versus wild type mice, demonstrating a protective effect of corin on AKI. In vitro overexpression of corin didn't directly alleviate hypoxia-induced HK-2 cells death, revealing that the protective effect of corin against AKI is not due to direct protection of tubular epithelial cells but may be through indirect protection. Microarray analysis showed enhanced inflammatory chemokines signaling and leukocyte chemotaxis in corin mice after AKI, identifying an important role of corin in halting leukocyte chemotaxis and inflammatory response. Consistently, corin mice after AKI displayed increased tubulointerstitial neutrophils and macrophages infiltration, as well as higher inflammatory mediators in kidneys. Taken together, our study indicates that tubular corin exerts a protective effect against AKI through negative regulation of chemotaxis signaling and inflammation in the kidney.