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Maternal vitamin D deficiency programmes adult renal renin gene expression and renal function

Published online by Cambridge University Press:  18 July 2013

A. C. Boyce ,
B. J. Palmer-Aronsten ,
M. Y. Kim  and
K. J. Gibson
A. C. Boyce
Affiliation:
Department of Physiology, School of Medical Sciences, The University of New South Wales, Sydney 2052, Australia
B. J. Palmer-Aronsten
Affiliation:
Department of Physiology, School of Medical Sciences, The University of New South Wales, Sydney 2052, Australia
M. Y. Kim
Affiliation:
Department of Physiology, School of Medical Sciences, The University of New South Wales, Sydney 2052, Australia
K. J. Gibson*
Affiliation:
Department of Physiology, School of Medical Sciences, The University of New South Wales, Sydney 2052, Australia
*
*Address for correspondence: K. J. Gibson, Department of Physiology, School of Medical Sciences, The University of New South Wales, Sydney 2052, Australia. (Email [email protected])
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Abstract

Renin is essential for renal development and in adult kidneys vitamin D deficiency increases renin gene expression. We aimed to determine whether maternal vitamin D deficiency upregulates fetal renal renin expression, and if this is sustained. We also examined growth and the long-term renal effects in offspring on a normal diet. Female Sprague–Dawley rats in UVB-free housing were fed either vitamin D deficient chow (DEF) or normal chow from 4 weeks and mated with vitamin D replete males at 10 weeks. Fetuses were collected at E20 or dams littered and the pups were weaned onto normal chow. Kidney mRNA levels for renin, (pro)renin receptor [(P)RR], transforming growth factor β 1 (TGF-β1), and nephrin were determined in E20 fetuses and in male offspring at 38 weeks. Renal function was assessed at 33 weeks (24 h, metabolic cage) in both sexes. Renal mRNA expression was upregulated for renin in fetuses (P < 0.05) and was almost doubled in adult male offspring from DEF dams (P < 0.05). Adult males had reduced creatinine clearance, solute excretion and a suppressed urinary sodium-to-potassium ratio (P < 0.05). Female adult DEF offspring drank more and excreted more urine (P < 0.05) but creatinine clearance was not impaired. We conclude that maternal vitamin D depletion upregulates fetal renal renin gene expression and this persists into adulthood where, in males only, there is evidence of sodium retention and compromised renal function. Importantly these effects occurred despite the animals being on a normal diet from the time of weaning onwards.

Keywords

developmentkidneyrenin–angiotensin systemvitamin D
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 5 , October 2013 , pp. 368 - 376
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

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References

1.Lips, P. Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol. 2010; 121, 297–300.Google Scholar
2.Bowyer, L, Catling-Paul, C, Daimond, T, et al. Vitamin D, PTH and calcium levels in pregnant women and their neonates. Clin Endocrinol. 2009; 70, 372–377.CrossRefGoogle ScholarPubMed
3.Dawodu, A, Wagner, CL. Mother–child vitamin D deficiency: an international perspective. Arch Dis Child. 2007; 92, 737–740.CrossRefGoogle ScholarPubMed
4.Johnson, JA, Grande, JP, Roche, PC, et al. 1 alpha, 25-dihydroxyvitamin D3 receptor ontogenesis in fetal renal development. Am J Physiol Renal Physiol. 1995; 269, F419–F428.Google Scholar
5.Yuan, W, Pan, W, Kong, J, et al. 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem. 2007; 282, 29821–29830.CrossRefGoogle ScholarPubMed
6.Li, YC, Kong, J, Wei, M, et al. 1,25-dihydroxyvitamin D3 is a negative endocrine regulator of the renin–angiotensin system. J Clin Invest. 2002; 110, 229–238.Google Scholar
7.Zhou, C, Lu, F, Cao, K, et al. Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin–angiotensin system in 1α-hydroxylase knockout mice. Kidney Int. 2008; 74, 170–179.Google Scholar
8.Nguyen, G, Delarue, F, Burcklé, C, et al. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest. 2002; 109, 1417–1427.Google Scholar
9.Huang, Y, Wongamorntham, S, Kasting, J, et al. Renin increases mesangial cell TGF–β1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms. Kidney Int. 2006; 69, 105–113.CrossRefGoogle ScholarPubMed
10.Welsh, WI, Saleem, MA. Nephrin – signature molecule of the glomerular podocyte? J Pathol. 2010; 220, 328–337.Google Scholar
11.Deb, DK, Wang, Y, Zhang, Z, et al. Molecular mechanism underlying 1,25-dihydroxyvitamin D regulation of nephrin gene expression. J Biol Chem. 2011; 286, 32011–32017.CrossRefGoogle Scholar
12.Guron, G, Friberg, P. An intact renin–angiotensin system is a prerequisite for normal renal development. J Hypertens. 2000; 18, 123–137.Google Scholar
13.Moritz, KM, Wintour, EM, Black, MJ, Bertram, JF, Caruna, G. Factors influencing mammalian kidney development: implications for health in adult life. Adv Anat Embryol Cell Biol. 2008; 196, 1–78.Google ScholarPubMed
14.Vehaskari, VM, Woods, LL. Prenatal programming of hypertension: lessons from experimental models. J Am Soc Nephrol. 2005; 16, 2545–2556.Google Scholar
15.Maka, N, Makrakis, J, Parkington, HC, et al. Vitamin D deficiency during pregnancy and lactation stimulates nephrogenesis in rat offspring. Pediatr Nephrol. 2008; 23, 55–61.Google Scholar
16.Gezmish, O, Tare, M, Parkington, HC, et al. Maternal Vitamin D deficiency leads to cardiac hypertrophy in rat offspring. Reprod Sci. 2010; 17, 168–176.Google Scholar
17.Tare, M, Emmett, SJ, Coleman, HA, et al. Vitamin D insufficiency is associated with impaired vascular endothelial and smooth muscle function and hypertension in young rats. J Physiol. 2011; 19, 4777–4786.CrossRefGoogle Scholar
18.Nascimento, FAM, Ceciliano, TC, Aguila, MB, Mandarim-de-Lacerda, CA. Maternal vitamin D deficiency delays glomerular maturity in F1 and F2 offspring. PLoS One. 2012; 7(8), e41740.Google Scholar
19.Rogers, SA, Droege, D, Dusso, A, Hammerman, MR. Incubation of metanephroi with Vitamin D3 increases number of glomeruli. Organogenesis. 2004; 1, 52–54.Google Scholar
20.Weishaar, RE, Simpson, RU. Vitamin D3 and cardiovascular function in rats. J Clin Invest. 1987; 79, 1706–1712.Google Scholar
21.Haeckel, R. Simplified determinations of the ‘true’ creatinine concentration in serum and urine. J Clin Chem Clin Biochem. 1980; 18, 385–394.Google Scholar
22.Lowry, OH, Rosebrough, NJ, Farr, LA, Randall, RJ. Protein measurement with the Folin reagent. J Biol Chem. 1951; 193, 265–275.CrossRefGoogle Scholar
23.Zhang, Z, Zhang, Y, Ning, G, et al. Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase. Proc Natl Acad Sci USA. 2008; 105, 15896–15901.Google Scholar
24.Weng, S, Sprague, JE, Jisu, O, et al. Vitamin D Deficiency Induces High Blood Pressure and Accelerates Atherosclerosis in Mice. PLoS One. 2013; 8, e54625.CrossRefGoogle ScholarPubMed
25.Gomez, RA, Lynch, KR, Sturgill, BC, et al. Distribution of renin mRNA and its protein in the developing kidney. Am J Physiol Renal Physiol. 1989; 257, F850–F858.Google Scholar
26.Castrop, H, Hocherl, K, Kurtz, A, et al. Physiology of kidney renin. Physiol Rev. 2010; 90, 607–673.Google Scholar
27.Kobori, H, Nangaku, M, Navar, LG, Nishiyama, A. The intrarenal renin–angiotensin system: From physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007; 59, 251–287.CrossRefGoogle Scholar
28.Stevens, LA, Coresh, J, Greene, T, Levey, AS. Assessing kidney function – measured and estimated glomerular filtration rate. N Engl J Med. 2006; 354, 2473–2483.Google Scholar
29.Kong, J, Zhang, Z, Li, D, et al. Loss of vitamin D receptor produces polyuria by increasing thirst. J Am Soc Nephrol. 2008; 19, 2396–2405.Google Scholar
30.Eyles, DW, Feron, F, Cui, X, et al. Developmental vitamin D deficiency causes abnormal brain development. Psychoneuroendocrinology. 2009; 34(Suppl 1), S247–S257.Google Scholar
31.Boldo, A, Campbell, P, Luthra, P, White, WB. Should the concentration of vitamin D be measured in all patients with hypertension? J Clin Hypertens. 2010; 12, 149–152.Google Scholar
32.Narvaez, CJ, Matthews, D, Broun, E, Chan, M, Welsh, JE. Lean phenotype and resistance to diet-induced obesity in vitamin D receptor knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue. Endocrinology. 2009; 150, 651–661.Google Scholar