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Articles in PresS, published online ahead of print October 22, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00277.2002
Submitted on August 2, 2002
Accepted on October 10, 2002
1 Department of Internal Medicine, YanBian University Medical College, 133000 YanJi, JiLin, China; Department Internal Medicine, The Catholic University of Korea, Seoul, Korea, Republic of
2 Department Internal Medicine, The Catholic University of Korea, Seoul, Korea, Republic of
3 Department of Anatomy, The Catholic University of Korea, Seoul, Korea, Republic of
4 Legacy Good Samaritan Hospital, Cellular Transplantation Division, Portland, Oregen, USA
* To whom correspondence should be addressed. E-mail: yanch{at}catholic.ac.kr.
Renal interstitial inflammation is an important factor in the pathogenesis of chronic cyclosporine A (CsA) nephropathy. We studied the expression of the chemoattractant, osteopontin (OPN), and the relationship between OPN expression and tubulointerstitial injury in a rat model of chronic CsA nephropathy. Chronic CsA nephropathy was induced in Sprague-Dawley rats by administering CsA (15 mg/kg s.c.) for 5 weeks, and then withdrawing it for 5 or 10 weeks. Renal function, histopathology (arteriolopathy, ED-1-positive cells, and tubulointerstitial fibrosis), renin-angiotensin system (RAS) activity, and OPN expression were observed during the follow-up period. Renal function deteriorated in CsA-treated rats, with the development of typical histopathology, and activation of RAS. After CsA withdrawal, these parameters were significantly reversed (all P < 0.05). The upregulation of OPN mRNA and protein expression seen in CsA-treated rat kidneys was decreased 5 weeks after CsA withdrawal, and was further decreased after 10 weeks. Of note, OPN mRNA expression correlated with the number of infiltrating macrophage (r = 0.651, P < 0.01) and tubulointerstitial fibrosis (r = 0.729, P < 0.01). These findings suggest that OPN expression and macrophage infiltration decrease after long-term CsA withdrawal in rats with established chronic CsA nephropathy, and this is closely associated with recovery from renal injury.
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