Abstract
Plasma membrane calcium pump isoform 1 (PMCA1) is encoded by ATPase plasma membrane Ca 2+ transporting 1 (ATP2B1), 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.
Highlights
Recent advances in genetic analysis techniques have enabled genome-wide association studies (GWASs)
We investigated blood pressure and renal PMCA1 expression in three, relatively unrelated, kidney disease models: ureteral obstruction (UUO), which induces kidney fibrosis; 5/6 nephrectomy, which causes reduced renal function; and chronic angiotensin II (Ang II) administration, which leads to albuminuria
Compared with in control mice, renal PMCA1 expression was not affected in the UUO and 5/6 nephrectomy models, but was significantly higher in the chronic Ang II administration model
Summary
Recent advances in genetic analysis techniques have enabled genome-wide association studies (GWASs). ATPase plasma membrane Ca2+ transporting 1 (ATP2B1) was associated with susceptibility to hypertension and GWASs, analyzing approximately 200,000 subjects worldwide, indicated that ATP2B1 is the most likely candidate gene responsible for hypertension (Yatsu et al 2007; International Consortium for Blood Pressure Genome-Wide Association Studies, 2011). PMCA1 is a housekeeping gene expressed in many organs, including brain, heart, blood vessels, and kidneys (Caride et al 1998; Strehler and Zacharias 2001). Studies on regulation of PMCA1 expression in rat kidneys reported that the amount of PMCA1 expressed by mesangial cells decreased with age (Rouse et al 1997). There have been very few reports describing regulation of renal expression of PMCA1 under various pathological conditions
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