Role of chemokine CXC-ligand 16 in renal fibrosis following renal ischemia-reperfusion injury in mice

Abstract

Objective To evaluate the role of chemokine CXC-ligand 16(CXCL16) in renal fibrosis following renal ischemia-reperfusion(I/R) injury in mice. Methods Twenty-four healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-30 g, were divided into 4 groups(n=6 each) using a random number table method: sham operation group(group S), sham operation plus anti-CXCL16 antibody group (group S+ A), group I/R, and I/R plus anti-CXCL16 antibody group(group I/R+ A). Renal ischemia was induced by occlusion of the left renal artery for 30 min followed by 72-h reperfusion, and the right kidney was removed on 5th day in anesthetized mice. CXCL16 antibody 5 mg/kg and the equal volume of normal saline were intraperitoneally injected at 72 h after reperfusion twice a week for 2 consecutive weeks in I/R+ A and I/R groups, respectively. Sham operation was performed, and the equal volume of CXCL16 antibody 5 mg/kg and normal saline were intraperitoneally injected at 72 h after reperfusion twice a week for 2 consecutive weeks in S+ A and S groups, respectively. Orbital venous blood samples were collected at day 14 after reperfusion for determination of serum blood urea nitrogen(BUN) and creatinine(Cr) concentrations. Animals were then sacrificed and the left kidney was removed for measurement of the renal fibrosis size(using Sirius red staining), expression of α-smooth muscle actin(α-SMA), fibronectin(FN) and type Ⅰ collagen(Col-Ⅰ) in renal tissues by Western blot. Results Compared with group S, the serum BUN and Cr concentrations and renal fibrosis size were significantly increased, and the expression of α-SMA, FN and Col-Ⅰ was up-regulated in group I/R(P<0.05). Compared with group I/R, the serum BUN and Cr concentrations and renal fibrosis size were significantly decreased, and the expression of α-SMA, FN and Col-Ⅰ was down-regulated in group I/R+ A(P<0.05). Conclusion CXCL16 is involved in the process of renal fibrosis following renal I/R injury in mice. Key words: Chemokines, CXC; Kidney; Reperfusion injury; Fibrosis