Wild-type mice reconstituted with bone marrow lacking the angiotensin II type 1 receptor developed significantly more severe renal interstitial fibrosis 14 days after ureteral obstruction compared to controls.
Does the absence of Agtr1 on bone marrow-derived macrophages worsen renal fibrosis in a mouse model of unilateral ureteral obstruction?
The absence of the angiotensin II type 1 receptor on bone marrow-derived macrophages exacerbates renal fibrosis during urinary tract obstruction, likely due to impaired macrophage phagocytic capability.
Absolute Event Rate: 139% vs 93%
p-value: p=<0.005
We examined the in vivo function of the angiotensin II type 1 receptor (Agtr1) on macrophages in renal fibrosis. Fourteen days after the induction of unilateral ureteral obstruction (UUO), wild-type mice reconstituted with marrow lacking the Agtr1 gene (Agtr1 -/-) developed more severe interstitial fibrosis with fewer interstitial macrophages than those in mice reconstituted with Agtr1 +/+ marrow. These differences were not observed at day 5 of UUO. The expression of profibrotic genes -including TGF-1, 1(I) collagen, and 1(III) collagen -was substantially higher in the obstructed kidneys of mice with Agtr1 -/-marrow than in those with Agtr1 +/+ marrow at day 14 but not at day 5 of UUO. Mice with Agtr1 -/-marrow were characterized by reduced numbers of peripheral-blood monocytes and macrophage progenitors in bone marrow. In vivo assays revealed a significantly impaired phagocytic capability in Agtr1 -/-macrophages. In vivo treatment of Agtr1 +/+ mice with losartan reduced phagocytic capability of Agtr1 +/+ macrophages to a level comparable to that of Agtr1 -/-macrophages. Thus, during urinary tract obstruction, the Agtr1 on bone marrow-derived macrophages functions to preserve the renal parenchymal architecture, and this function depends in part on its modulatory effect on phagocytosis.
Nishida et al. (Sun,) conducted a other in Renal fibrosis (n=37). Agtr1-/- bone marrow transplantation vs. Agtr1+/+ bone marrow transplantation was evaluated on Interstitial collagen fractional volume (points per 1000) at 14 days after unilateral ureteral obstruction (p=<0.005). Wild-type mice reconstituted with bone marrow lacking the angiotensin II type 1 receptor developed significantly more severe renal interstitial fibrosis 14 days after ureteral obstruction compared to controls.
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