HO-1 knockdown upregulates the expression of VCAM-1 to induce neutrophil recruitment during renal ischemia-reperfusion injury

Heme oxygenase-1 (HO-1) has been reported to be upregulated following renal ischemia-reperfusion injury (IRI) and plays a key cytoprotective role; however, the underlying molecular mechanisms of its protective effects remain poorly understood. In the present study, in order to further elucidate the molecular mechanisms underlying the cytoprotective role of HO-1 in renal IRI, HO-1(+/+) and HO-1(+/−) mice were subjected to renal ischemia and subsequent reperfusion followed by the analysis of blood urea nitrogen (BUN) and serum creatinine (SCr) levels, the severity of histological changes, HO-1 and vascular cell adhesion molecule-1 (VCAM-1) protein expression, the mRNA expression of inflammatory factors and the effects of VCAM-1 blockade. The results of the present study demonstrated that the upregulated expression levels of VCAM-1 in HO-1(+/−) mice during IRI increased the extent of renal tissue damage and activated the inflammatory response. These effects were subsequently reversed following infusion with an anti-VCAM-1 antibody. In addition, the upregulated expression of VCAM-1 in mouse glomerulus vascular endothelial cells isolated from HO-1(+/−) mice increased the adhesion and migration of neutrophils, effects which were also reversed upon incubation with an anti-VCAM-1 antibody. These results indicated that HO-1 knockdown may upregulate the expression of VCAM-1 during renal IRI, resulting in increased neutrophil recruitment and the activation of the inflammatory response, thereby exacerbating renal IRI. The present study thus highlights the regulatory mechanisms of HO-1 in renal IRI and provides a potential target for the clinical treatment of IRI following renal transplantation.