Enhanced expression of bone morphogenetic protein system in aldosterone-treated mouse kidneys
Enhanced expression of bone morphogenetic protein system in aldosterone-treated mouse kidneys
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DOI：
10.1038/hr.2011.186
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发表时间：
2012-03
影响因子：
5.4
通讯作者：
J. Suzuki;F. Otsuka;Y. Matsumoto;K. Inagaki;T. Miyoshi;M. Takeda;Naoko Tsukamoto;Eri Nakamura;Kanako Ogura;H. Makino
中科院分区：
文献类型：
--
作者：
J. Suzuki;F. Otsuka;Y. Matsumoto;K. Inagaki;T. Miyoshi;M. Takeda;Naoko Tsukamoto;Eri Nakamura;Kanako Ogura;H. Makino
最近的研究表明，骨形态发生蛋白（BMP），特别是BMP-7，在各种肾脏疾病的发展中具有抑制作用。我们曾报道骨形成蛋白对醛固酮诱导的肾小球系膜细胞增殖的拮抗作用。在本研究中，我们研究了在体内的作用，骨形成蛋白在醛诱导的肾小球损伤。6周龄BALB/c小鼠经腹腔注射Aldo（5 μg/d）和/或口服高盐（2%）水治疗9周。全身血压，体重，肾脏重量和每日蛋白尿没有显着改变，奥尔多和/或高盐治疗。然而，肾组织学检查显示，在Aldo注射液和高盐给药组中，肾小球细胞构成和肾小球直径增加。免疫组化显示BMP-4和BMP-7在肾小球系膜区表达。Aldo通过盐皮质激素受体（MR）刺激系膜细胞增殖和增加细胞外基质而引起肾小球损伤。肾皮质MR信使RNA（mRNA）的表达短暂增加3周的治疗与Aldo和高盐摄入，但减少9周的治疗。此外，BMP-4和BMP-7 mRNA的表达水平在Aldo和高盐给药处理的肾皮质中增强。提示Aldo在高盐环境下激活了肾脏BMP系统，可能在体内对抗肾小球损伤中发挥重要作用。
Recent studies have shown that bone morphogenetic proteins (BMPs), particularly BMP-7, have an inhibitory role in the development of various renal diseases. We previously reported antagonistic effects of BMPs on renal mesangial cell proliferation induced by aldosterone (Aldo) in vitro. In the present study, we investigated in vivo roles of BMPs in Aldo-induced renal glomerular injury. BALB/c mice aged 6 weeks were treated with Aldo injection (5 μg per day, intraperitoneally) and/or oral administration of high-salt (2%) water for 9 weeks. Systemic blood pressure, body weight, kidney weight and daily proteinuria were not significantly changed by Aldo and/or high-salt treatment. However, renal histological examination revealed increases in glomerular cellularity and glomerular diameter in the groups treated with Aldo injection and high-salt administration. Immunohistochemistry demonstrated expression of BMP-4 and-7 in the glomerular mesangial region. Aldo causes renal glomerular damage by stimulating mesangial cell proliferation and increasing extracellular matrix via the mineralocorticoid receptor (MR). MR messenger RNA (mRNA) expression in the renal cortex was transiently increased by 3-week treatment with Aldo and high-salt intake, but was decreased by 9-week treatment. Furthermore, the expression levels of BMP-4 and-7 mRNA were enhanced in the renal cortex treated with Aldo and high-salt administration. These findings suggest that the renal BMP system is activated by Aldo under the condition of high-salt exposure, which may have a key role in antagonizing glomerular damage in vivo.