Renal damage inhibited in mice lacking angiotensinogen gene subjected to unilateral ureteral obstruction.
OBJECTIVE
To determine how angiotensin II (Ang II) contributes to renal interstitial fibrosis, the inflammatory response, and tubular cell apoptosis and proliferation in unilateral ureteral obstruction using mice genetically deficient in angiotensinogen (Agt(-/-)).


METHODS
The left kidney of wild-type mice (WT; C57BL/6) and Agt(-/-) mice was obstructed for 2 weeks, and then both kidneys were harvested. The serum Ang II levels were determined by radioimmunoassay. The expression of transforming growth factor-beta in renal tissue was assessed using enzyme-linked immunosorbent assay. The renal tissue was stained with Masson's trichrome. Renal tubular proliferation and apoptosis was detected by immunostaining for proliferating cell nuclear antigen and single-stranded DNA, respectively. Interstitial leukocyte and macrophage infiltration was investigated by immunostaining for CD45 and F4/80, respectively.


RESULTS
The serum Ang II levels in the Agt(-/-) mice were significantly lower than those in the WT mice (P < .01), and tissue transforming growth factor-beta in the obstructed kidney of Agt(-/-) mice was significantly lower than that in WT mice (P < .05). Interstitial collagen deposition was significantly lower in the Agt(-/-) obstructed kidneys than in the WT obstructed kidneys (P < .01). Tubular proliferation was significantly greater and tubular apoptosis was significantly lower in the Agt(-/-) obstructed kidneys than in the WT obstructed kidneys (P < .01 and P < .01, respectively). Interstitial infiltration by leukocytes and macrophages was significantly lower in the Agt(-/-) obstructed kidneys than in the WT obstructed kidneys (P < .01 and P < .01, respectively).


CONCLUSIONS
The results of the present study support the targeting of Ang II as a reasonable approach by which to prevent renal tissue damage in unilateral ureteral obstruction.
Uchida
Yasumitsu
Y
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Miyajima
Akira
A
Kikuchi
Eiji
E
Kozakai
Norihide
N
Kosaka
Takeo
T
Ieda
Masaki
M
Fukuda
Keiichi
K
Ohigashi
Takashi
T
Oya
Mototsugu
M
D000804:Angiotensin II / Q000235:genetics* / Q000502:physiology; D000808:Angiotensinogen / Q000235:genetics* / Q000502:physiology; D000818:Animals; D005260:Female; D005355:Fibrosis; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D014517:Ureteral Obstruction / Q000150:complications* / Q000235:genetics*
D000808:Angiotensinogen; D000804:Angiotensin II