[Regulatory Effect of Vitamin D on Renin Expression at Maternal-Fetal Interface].
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition(2022)
摘要
Objective: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, cyp27 b1, cyp24 a1, 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.
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关键词
Decidua,Preeclampsia,Renin,Vitamin D
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