Renal Damage Inhibited in Mice Lacking Angiotensinogen Gene Subjected to Unilateral Ureteral Obstruction

Yasumitsu Uchida, Akira Miyajima, Eiji Kikuchi, Norihide Kozakai, Takeo Kosaka, Masaki Ieda, Keiichi Fukuda, Takashi Ohigashi, Mototsugu Oya

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Abstract

Objectives: 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-β 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-β 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.

Original languageEnglish
Pages (from-to)938-943
Number of pages6
JournalUrology
Volume74
Issue number4
DOIs
Publication statusPublished - 2009 Oct 1

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ASJC Scopus subject areas

  • Urology

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