AT1A-mediated activation of kidney JNK1 and SMAD2 in obstructive uropathy: Preservation of kidney tissue mass using candesartan

Ann Wamsley-Davis, Ranjit Padda, Luan Truong, Chun Chui Tsao, Ping Zhang, David Sheikh-Hamad

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Literature suggests the involvement of the renin-angiotensin system and transforming growth factor (TGF)-β in the renal injury that follows chronic ureteric obstruction. SMAD proteins and the JNK1 cascade are essential components of TGF-β signaling machinery, and recent data suggest cooperative interaction between JNK1 and SMAD proteins in TGF-β-mediated gene expression. We used a rat model of chronic unilateral ureteric obstruction to study the effects of candesartan, an AT1A-receptor blocker, on tissue morphology and the activities of JNK1 and SMAD2 protein in the kidney. Ureteric obstruction for 28 days leads to interstitial fibrosis, tubule atrophy, and marked activation of SMAD2 and JNK1, without significant change in p38 kinase or ERK. Candesartan treatment, however, attenuated the chronic tubulointerstitial injury in obstructed kidneys and was associated with significant preservation of kidney tissue mass. Furthermore, treatment with candesartan diminished JNK1 activity and downregulated SMAD2 protein and activity in obstructed kidneys. In conclusion, obstructed kidneys showed chronic tubulointerstitial injury, which was associated with JNK1 and SMAD2 activation. The renoprotective effects afforded by AT1A-receptor blockade in obstructive uropathy are consistent with attenuation of JNK1- and SMAD2-mediated renal injury.

Original languageEnglish (US)
Pages (from-to)F474-F480
JournalAmerican Journal of Physiology - Renal Physiology
Issue number3 56-3
StatePublished - Sep 2004


  • AT; angiotensin II
  • MAPK
  • Monocyte chemotactic protein-1
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology


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