Regulatory Effect of Vitamin D on Renin Expression at Maternal-Fetal Interface

CHEN Chun-yan, ZHENG Li-bin, WANG Yan-ling, LI Xun, ZHANG Xue-qin, CAO Bin

Abstract

To investigate the regulatory effect and mechanism of vitamin D on the local renin-angiotensin system at maternal-fetal interface in the pathological process of preeclampsia (PE).   Methods  The mRNA and protein expression of renin in decidua of normal pregnancy and PE placentas was determined by RT-PCR and Western blot. Normal decidual tissues were treated with active and inactive vitamin D for 48 h in vitro and the expressions of renin and vitamin D deactivating enzyme CYP24A1 were determined by RT-PCR and Western blot. Normal decidual stromal cells and glandular epithelial cells were isolated and purified, and identified by immunocytochemical staining. RT-PCR was used to examine the mRNA of vdr, cyp27b1, cyp24a1, and renin in the two types of cells and in decidual tissue, and the mRNA products were subjected to gel electrophoresis. These two cell types were treated with active and inactive vitamin D in vitro and the expressions of renin and vitamin D deactivating enzyme CYP24A1 were determined by RT-PCR and Western blot. Decidual gland epithelial cells were treated with protein kinase A (PKA) activator forskolin or inhibitor H89 to explore the interaction between PKA pathway and vitamin D in the regulation of renin expression.   Results  The expression of renin in PE decidua was significantly higher than that of normal control at transcriptional and translational levels (P<0.05). Vitamin D treatment could significantly down-regulate the expression of renin in normal decidua tissues (P<0.05), while it significantly up-regulated CYP24A1 expression (P<0.001). Decidual stromal cells and gland epithelial cells were successfully isolated from decidual tissue. Compared with that in decidual stromal cells, the mRNA level of vitamin D-related molecules in gland epithelial cells was more similar to that in decidual tissue. Active or inactive vitamin D treatment significantly inhibited the expression of renin in glandular epithelial cells (P<0.05), but the expression of renin in decidual stromal cells was not affected. However, the treatment of active or inactive vitamin D in these two kinds of cells significantly increased the expression of CYP24A1 (P<0.001). Active vitamin D could significantly inhibit the upregulation of renin by PKA agonist forskolin, and could inhibit the expression of renin through synergy with PKA inhibitor H89.   Conclusion  The expression of renin in placental decidua is up-regulated in patients with PE, and the activation of local renin-angiotensin system at the maternal-fetal interface may be involved in the pathogenesis of PE. Vitamin D can specifically down-regulate renin expression in human decidual gland epithelial cells by competing with the PKA pathway. Vitamin D supplementation may have potential value for clinical intervention of PE.

 

Keywords: Vitamin D, Preeclampsia, Renin, Decidua

 

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References


RANA S， LEMOINE E， GRANGER J P， et al. Preeclampsia: Pathophysiology, challenges, and perspectives. Circ Res，2019，124(7): 1094–1112.

ABDELRAHIEM S K， AHMED A B A， SHARIF M E， et al. Association between maternal serum 25-hydroxyvitamin D concentrations and the risk of pre-eclampsia in central Sudan: A case-control study. Trans R Soc Trop Med Hyg，2022，116(5): 487–491.

JIN C H， PIKE J W. Human vitamin D receptor-dependent transactivation in Saccharomyces cerevisiae requires retinoid X receptor. Mol Endocrinol，1996，10(2): 196–205.

CHRISTAKOS S， DHAWAN P， VERSTUYF A， et al. Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev，2016，96(1): 365–408.

SAPONARO F， SABA A， ZUCCHI R. An Update on vitamin D metabolism. Int J Mol Sci，2020，21(18): 6573.

KARRAS S N， WAGNER C L， CASTRACANE V D. Understanding vitamin D metabolism in pregnancy: From physiology to pathophysiology and clinical outcomes. Metabolism，2018，86: 112–123.

AJABSHIR S， ASIF A， NAYER A. The effects of vitamin D on the renin-angiotensin system. J Nephropathol，2014，3(2): 41–43.

DE LA GUIA-GALIPIENSO F ， MARTINEZ-FERRAN M， VALLECILLO N， et al. Vitamin D and cardiovascular health. Clin Nutr， 2021，40(5): 2946–2957.

ZITOUNI H， RAGUEMA N， GANNOUN M B A， et al. Impact of obesity on the association of active renin and plasma aldosterone concentrations, and aldosterone-to-renin ratio with preeclampsia. Pregnancy Hypertens，2018，14: 139–144.

PONIEDZIALEK-CZAJKOWSKA E， MIERZYNSKI R. Could vitamin D be effective in prevention of preeclampsia? Nutrients，2021，13(11): 3854.

HOGAN M C， FOREMAN K J， NAGHAVI M， et al. Maternal mortality for 181 countries, 1980–2008: A systematic analysis of progress towards Millennium Development Goal 5. Lancet，2010，375(9726): 1609–1623.

ANTON L， MERRILL D C， NEVES L A， et al. Activation of local chorionic villi angiotensin Ⅱ levels but not angiotensin (1-7) in preeclampsia. Hypertension，2008，51(4): 1066–1072.

AGHAJAFARI F， NAGULESAPILLAI T， RONKSLEY P E， et al. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ， 2013， 346: f1169[2022-04-20]. https://doi. org/10.1136/bmj.f1169.

CAO Y， JIA X， HUANG Y， et al. Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia. Sci Rep，2021，11(1): 11168.

GANGULY A， TAMBLYN J A， FINN-SELL S， et al. Vitamin D, the placenta and early pregnancy: Effects on trophoblast function. J Endocrinol，2018，236(2): R93–R103.

SASSI F， TAMONE C， D'AMELIO P. Vitamin D: Nutrient, hormone, and immunomodulator. Nutrients，2018，10(11): 1656.

SEQUEIRA LOPEZ M L， GOMEZ R A. Novel mechanisms for the control of renin synthesis and release. Curr Hypertens Rep，2010，12(1): 26–32.

GOVENDER D， DAMJANOVIC L， GAZA C A， et al. Vitamin D decreases silencer methylation to downregulate renin gene expression. Gene， 2021， 786: 145623[2022-04-20]. https://doi.org/10.1016/j.gene. 2021.145623.

YUAN W， PAN W， KONG J， et al. 1, 25-dihydroxy vitamin 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(41): 29821–29830.


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