In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 284, No. 2 ( 2003-02-01), p. F389-F398
Abstract:
Renal interstitial inflammation is an important factor in the pathogenesis of chronic cyclosporin 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 sc) for 5 wk and then withdrawing it for 5 or 10 wk. 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 wk after CsA withdrawal and was further decreased after 10 wk. 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.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00277.2002
Language:
English
Publisher:
American Physiological Society
Publication Date:
2003
detail.hit.zdb_id:
1477287-5
