Abstract

Aim Vitamin D plays an important role in water and salt homeostasis. The aim of our study was to investigate the underlying relationship of Vitamin D and Aquaporins (AQP). Methods The behaviors of 1α (OH)-ase knockout mice and wild type mice were observed before analysis. The ICR mice were treated with vehicle or paricalcitol, a vitamin D analogue, followed by animals receiving a standard diet and free access to drinking water either with aliskiren (renin blocker; 37.5 mg aliskiren in 100 ml water), or telmisartan (a angiotensin II type I receptor blocker; 40 mg telmisartan in 100 ml water) a week before study. The expressions of AQP-1, AQP-4, and renin in mice kidneys were detected by western bolting, immunohistochemistry, and immunofluorescence. Results Diuresis and polydipsia were observed in 1α (OH)-ase knockout mice, and a decreased water intake and urine output in ICR mice was observed after paricalcitol treatment. Compared with wild type, the AQP-1 expressions were increased in renal papilla and AQP-4 expressions were decreased in renal proximal tubule of 1α(OH) ase knockout mice. In addition, AQP-1 was decreased in renal papilla and AQP-4 expressions were increased in proximal tubule by suppressing renin activity or supplement of Vitamin D analogue. After injecting renin into the lateral ventricle of the 1α(OH)ase knockout mice, the renin expression level was decreased in the kidney, followed by the decrease of AQP-1 in renal papilla and increase of AQP-4 in proximal tubule. Conclusions Overall, Vitamin D and renin inhibitors have synergistic effects in regulating water channels in mice kidneys.

Highlights

  • Vitamin D, a fat-soluble steroid hormone, plays an important role in regulating a number of biological functions [1]

  • The water intake and urine output of mice in ko group increased within 24 hours, and the volume of drinking water and urine was significantly decreased in pari group (Figure 1), suggesting that the Vitamin D/Vitamin D receptor (VDR) system plays a role in regulation of urine volume and water intake

  • There were no differences in the proximal tubules, the expressions of AQP-1 in the renal papilla of the 1α(OH)ase knockout mice were significantly increased compared with the wild type mice (Figure 2(c))

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Summary

Introduction

Vitamin D, a fat-soluble steroid hormone, plays an important role in regulating a number of biological functions [1]. The Vitamin D precursors, 7-dehydrocholesterol, are formed by ultraviolet irradiation in the skin and transported to liver. Hydroxy Vitamin D3, 25-hydroxyvitamin D3, is synthesized from 7-dehydrocholesterol by 25-cholcalciferol hydroxylase in the liver and is transported to kidney. 1,25-dihydroxyvitamin D3, the activity form of Vitamin D3, as an agonist of nuclear receptor super-family dihydroxyvitamin binds to Vitamin D receptor (VDR), which is a member of nuclear receptor super family and regulate gene expression by heterodimerizing with other members and translocating to nucleus and binding to nuclear response element [2]. The role of Vitamin D3 in calcium and phosphate metabolism [3], blood sugar control [4], lipid metabolism, salt excretion, and urine concentration is well established. We have demonstrated that VDR knockout mice cause polyuria and anadipsia [5]

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