Expression and mechanism of osteoactivin in the kidney of SD rats after acute cyclosporine A toxicity

Abstract

To determine the expression and mechanism of osteoactivin (OA) in the kidney by establishing SD rat model of acute cyclosporine A (CsA) toxicity. SD rats were fed with normal diet for a week, which they were then randomly divided into 3 groups: an experimental group (gavage with cycloporin A and olive oil), a vector group (gavage with olive oil), and a control group (gavage with normal saline). SD rats were killed 2 days, 1 week, or 2 weeks after the gavage to examine the serum creatinine (SCr) and body weight. HE staining was used to detect the kidney histopathological change. Immunohistochemistry was used to observe the staining degree and area of OA. Western blot was used to detect the OA protein.The mRNA expressions of the OA, matrix metalloproteinase-13(MMP-13), and collagen type III(Col III) were examined by RT-PCR. The body weight and SCr of the rats in the experimental group 1 week and 2 days after the gavage had no significant difference compared with the vector group or the control group (P>0.05).On the end of 2nd week, the rats' body weight was significantly reduced, and SCr significantly increased compared with the vector group or the control group (P<0.001).The main histopathological changes in the experimental group were inflammatory cell infiltration, vacuolar degeneration of interstitial cells, or tubular epithelial cell necrosis. Intense OA expression located in the tubular epithelium and interstitial fibroblasts in the kidney of the experimental group was observed by immunohistochemistry. After CsA gavage, the relative mRNA expressions of OA, MMP-13, and Col III significantly increased with time. Western blot did not find the expression of OA protein in the control and the vector group, which increased with time in the experimental group. OA expresses in the kidney of SD rats after acute CsA toxicity and mainly expresses in the tubular epithelial cells and renal interstitium. OA is more sensitive to the damage of kidney tissue caused by CsA than by SCr. The early-phase up-regulation of OA expression in the tubular epithelium in response to renal injury caused by acute CsA toxicity might play a key role in triggering the renal interstitial fibrosis via activating expression of MMPs and collagen remodeling in SD rats.