PMID- 10074479
OWN - NLM
STAT- MEDLINE
DCOM- 19990331
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 103
IP  - 5
DP  - 1999 Mar
TI  - Angiotensin II plays a pathogenic role in immune-mediated renal injury in mice.
PG  - 627-35
AB  - Several lines of evidence show the importance of angiotensin II (AII) in renal 
      injuries, especially when hemodynamic abnormalities are involved. To elucidate 
      the role of AII in immune-mediated renal injury, we studied anti-glomerular 
      basement membrane (GBM) nephritis in AII type 1a receptor (AT1a)-deficient 
      homozygous (AT1a-/-) and wild-type (AT1a+/+) mice. A transient activation of the 
      renin-angiotensin system (RAS) was observed in both groups of mice at around day 
      1. A renal expression of monocyte chemoattractant protein-1 (MCP-1) was 
      transiently induced at six hours in both groups, which was then downregulated at 
      day 1. In the AT1a+/+ mice, after RAS activation, the glomerular expression of 
      MCP-1 was exacerbated at days 7 and 14. Thereafter, severe proteinuria developed, 
      and the renal expressions of transforming growth factor-beta1 (TGF-beta1) and 
      collagen type I increased, resulting in severe glomerulosclerosis and 
      interstitial fibrosis. In contrast, glomerular expression of MCP-1, proteinuria, 
      and tissue damage were markedly ameliorated in the AT1a-/- mice. Because this 
      amelioration is likely due to the lack of AT1a, we can conclude that AII action, 
      mediated by AT1a, plays a pathogenic role in anti-GBM nephritis, in which AII may 
      contribute to the exacerbation of glomerular MCP-1 expression. These results 
      suggest the involvement of AII in immune-mediated renal injuries.
FAU - Hisada, Y
AU  - Hisada Y
AD  - Discovery Research Laboratory, Tanabe seiyaku Co., Ltd., Kashima, Osaka 532-8505, 
      Japan.
FAU - Sugaya, T
AU  - Sugaya T
FAU - Yamanouchi, M
AU  - Yamanouchi M
FAU - Uchida, H
AU  - Uchida H
FAU - Fujimura, H
AU  - Fujimura H
FAU - Sakurai, H
AU  - Sakurai H
FAU - Fukamizu, A
AU  - Fukamizu A
FAU - Murakami, K
AU  - Murakami K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, Angiotensin)
RN  - 0 (Transforming Growth Factor beta)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Angiotensin II/*immunology
MH  - Animals
MH  - Anti-Glomerular Basement Membrane Disease/*genetics/*immunology
MH  - Chemokine CCL2/immunology
MH  - Collagen/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, Angiotensin/*genetics/*immunology
MH  - Renin-Angiotensin System/*immunology
MH  - Transforming Growth Factor beta/immunology
PMC - PMC408115
EDAT- 1999/03/13 00:00
MHDA- 1999/03/13 00:01
PMCR- 1999/03/01
CRDT- 1999/03/13 00:00
PHST- 1999/03/13 00:00 [pubmed]
PHST- 1999/03/13 00:01 [medline]
PHST- 1999/03/13 00:00 [entrez]
PHST- 1999/03/01 00:00 [pmc-release]
AID - 02454 [pii]
AID - 10.1172/JCI2454 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Mar;103(5):627-35. doi: 10.1172/JCI2454.