Wakui Hiromichi, Sumida Koichiro, Fujita Megumi, Ohtomo Yuta, Ohsawa Masato, Kobayashi Ryu, Uneda Kazushi, Azushima Kengo, Haruhara Kotaro, Yatsu Keisuke, Hirawa Nobuhito, Minegishi Shintaro, Ishigami Tomoaki, Umemura Satoshi, Tamura Kouichi
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Physiol Rep. 2017 Jun;5(11). doi: 10.14814/phy2.13316.
Plasma membrane calcium pump isoform 1 (PMCA1) is encoded by (), the most likely candidate gene responsible for hypertension. Although PMCA1 is highly expressed in the kidney, little is known about regulation of its renal expression in various pathological conditions in vivo. Our study was designed to elucidate regulation of renal PMCA1 expression in mice. We employed three mouse models for kidney disease. These were the unilateral ureteral obstruction (UUO), the remnant kidney using 5/6 nephrectomy, and chronic angiotensin II administration models. Mice were assessed for systolic blood pressure and renal injury in accordance with the damage induced in the specific model. Kidney PMCA1 mRNA levels were measured in all mice. The UUO model showed renal fibrosis but no changes in blood pressure or renal PMCA1 mRNA expression. Similarly, the 5/6 nephrectomy model exhibited declined renal function without changes in blood pressure or renal PMCA1 mRNA expression. In contrast, chronic angiotensin II administration increased albuminuria and blood pressure as well as significantly increasing renal PMCA1 mRNA and protein expression. These results suggest that renal PMCA1 has a role as one of the molecules involved in angiotensin II-induced hypertension and kidney injury.
质膜钙泵同工型1(PMCA1)由()编码,是导致高血压最可能的候选基因。尽管PMCA1在肾脏中高度表达,但关于其在体内各种病理条件下肾脏表达的调控知之甚少。我们的研究旨在阐明小鼠肾脏中PMCA1表达的调控机制。我们采用了三种肾脏疾病小鼠模型。分别是单侧输尿管梗阻(UUO)模型、采用5/6肾切除的残肾模型以及慢性给予血管紧张素II模型。根据特定模型诱导的损伤情况对小鼠的收缩压和肾损伤进行评估。检测了所有小鼠肾脏中PMCA1 mRNA水平。UUO模型出现了肾纤维化,但血压和肾脏PMCA1 mRNA表达无变化。同样,5/6肾切除模型表现出肾功能下降,而血压和肾脏PMCA1 mRNA表达无变化。相比之下,慢性给予血管紧张素II增加了蛋白尿和血压,同时显著增加了肾脏PMCA1 mRNA和蛋白表达。这些结果表明,肾脏PMCA1作为参与血管紧张素II诱导的高血压和肾损伤的分子之一发挥作用。