Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis.
Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis.
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骨髓来源细胞中血管紧张素 II 1 型受体的缺失对于肾纤维化的进展是有害的。
DOI：
10.1172/jci15045
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Ichikawa,Iekuni
中科院分区：
文献类型：
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作者：
Nishida,Masashi;Fujinaka,Hidehiko;Matsusaka,Taiji;Price,James;Kon,Valentina;Fogo,AgnesB;Davidson,JeffreyM;Linton,MacRaeF;Fazio,Sergio;Homma,Toshio;Yoshida,Hiroaki;Ichikawa,Iekuni
我们研究了肾纤维化中巨噬细胞上血管紧张素II 1型受体（Agtr 1）的体内功能。在诱导单侧输尿管梗阻（UUO）后14天，用缺乏Agtr 1基因（Agtr 1-/-）的骨髓重建的野生型小鼠比用Agtr 1 +/+骨髓重建的小鼠发生更严重的间质纤维化，间质巨噬细胞更少。在UUO第5天未观察到这些差异。在UUO的第14天，Agtr 1-/-骨髓小鼠的梗阻肾脏中促纤维化基因（包括TGF-β1、α1（I）胶原和α1（III）胶原）的表达显著高于Agtr 1 +/+骨髓小鼠，但在第5天没有。Agtr 1-/-骨髓小鼠的特征是外周血单核细胞和骨髓中巨噬细胞祖细胞数量减少。体内实验显示Agtr 1-/-巨噬细胞的吞噬能力明显受损。在体内用氯沙坦治疗Agtr 1 +/+小鼠，可使Agtr 1 +/+巨噬细胞的吞噬能力降低到与Agtr 1-/-巨噬细胞相当的水平。因此，在尿路梗阻，骨髓来源的巨噬细胞上的Agtr 1功能，以保持肾实质结构，这种功能部分取决于其对吞噬作用的调节作用。
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 withAgtr1+/+marrow. These differences were not observed at day 5 of UUO. The expression of profibrotic genes — including TGF-β1, α1(I) collagen, and α1(III) collagen — was substantially higher in the obstructed kidneys of mice withAgtr1–/–marrow than in those withAgtr1+/+marrow at day 14 but not at day 5 of UUO. Mice withAgtr1–/–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 inAgtr1–/–macrophages. In vivo treatment ofAgtr1+/+mice with losartan reduced phagocytic capability ofAgtr1+/+macrophages to a level comparable to that ofAgtr1–/–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.