Aberrant endothelial expression of hnRNPC1/C2 and VDR and reduced maternal vitamin D levels in women with preeclampsia

作者：Gu, Yang; Lin, Shuai; Morgan, John A.; Lewis, David F.; Wang, Yuping^*

来源：Journal of Steroid Biochemistry and Molecular Biology, 2022, 222: 106155.

DOI：10.1016/j.jsbmb.2022.106155

• HnRNPC1/C2
• VDR
• Vitamin D
• Endothelial cells
• Pregnancy
• Preeclampsia

Vitamin D deficiency is a widespread health problem globally and vitamin D deficiency/ insufficiency in preg-nancy is a risk factor for preeclampsia, a hypertensive disorder in human pregnancy. Vitamin D elicits its bio-logical effects through binding to its receptor VDR. In the present study, we determined maternal vascular expression of VDR and hnRNPC1/C2, a native repressor of VDR, in subcutaneous adipose tissue from women with normal pregnancy and preeclampsia. Maternal antenatal and postnatal vitamin D levels were measured. We found that hnRNPC1/C2 expression was markedly increased, while VDR expression was markedly reduced, in maternal vessel endothelium and smooth muscle cells from women with preeclampsia compared to that from normal pregnant controls. Reduced VDR expression was relevant to low maternal antenatal and postnatal vitamin D levels in women with preeclampsia. Using human umbilical vein endothelial cells (HUVECs) as an endothelial model, we further investigated the role of hnRNPC1/C2-mediated VDR expression in endothelial cells, and tested effect of hnRNPC1/C2 inhibition on endothelial response to bioactive vitamin D, 1,25(OH)2D3. Our results showed that inhibition of hnRNPC1/C2 by hnRNPC1/C2 siRNA resulted in not only an increase in endothelial VDR expression, but further improved endothelial response to 1,25(OH)2D3. These findings indicate that aberrant hnRNPC1/C2 expression may contribute to reduced vascular expression of VDR in women with preeclampsia and suggest that hnRNPC1/C2 could be a target for improving vascular endothelial cell response to vitamin D.

• 单位
  1; 哈尔滨医科大学