Pathological expression of renin and angiotensin II in the renal tubule after subtotal nephrectomy. Implications for the pathogenesis of tubulointerstitial fibrosis.
The finding that the systemic renin-angiotensin system (RAS) is not activated in most types of chronic renal disease has led to the suggestion that a local, intrarenal RAS may be an important determinant in the relentless progression of renal disease. Therefore, cell specific changes in various components of the RAS in response to renal mass reduction and angiotensin converting enzyme (ACE) inhibition were examined. Thirty Sprague-Dawley rats were randomly assigned to sham surgery, subtotal nephrectomy (STNx) alone or STNx treated with the ACE inhibitor, perindopril, and sacrificed after 12 weeks. In sham rats, renin mRNA and protein were only present in the juxtaglomerular apparatus. In contrast, in STNx kidneys, renin and angiotensin II expression were noted predominantly in renal tubular epithelial cells in association with overexpression of the prosclerotic cytokine, transforming growth factor-beta1 (TGF-beta1). In perindopril-treated STNx rats expression of renin and TGF-beta1 were similar to control animals. These finding indicate that following renal mass reduction there is pathological tubular expression of various components of the RAS. Furthermore, in contrast to the juxtaglomerular apparatus, tubular renin expression was reduced with ACE inhibition. These changes within the intrarenal RAS may be pathogenetically linked to the development of tubulointerstitial injury.
Gilbert
R E
RE
Department of Medicine, University of Melbourne, Australia. gilbert@austin.unimelb.edu.au
Wu
L L
LL
Kelly
D J
DJ
Cox
A
A
Wilkinson-Berka
J L
JL
Johnston
C I
CI
Cooper
M E
ME
D000804:Angiotensin II / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000033:anatomy & histology / Q000473:pathology / Q000601:surgery; D007684:Kidney Tubules / Q000033:anatomy & histology / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D009392:Nephrectomy; D009395:Nephritis, Interstitial / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000032:analysis / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism
D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; D012083:Renin