Kamboj Kajal, Kumar Vivek, Yadav Ashok Kumar
Departments of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Int J Mol Sci. 2025 Apr 23;26(9):3967. doi: 10.3390/ijms26093967.
Vitamin D has been shown to improve immunity as well as vascular function. We investigated the effect of cholecalciferol on T-cell phenotype in cultured peripheral blood mononuclear cells (PBMCs) from twenty vitamin D-deficient, non-diabetic chronic kidney disease (CKD) subjects. We also studied vitamin D effects on endothelial and vascular function markers in human aortic endothelial cells (HAECs) and in human aortic smooth muscle cells (HASMCs), respectively. We studied endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinase 38 (p38 Map kinase), protein kinase B (Akt), and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) in HAECs and α-smooth muscle actin (α-SMA), smooth muscle calponin (SM-Calponin), smooth muscle myosin heavy chain (SM-MHC), and calcium-sensing receptor (CaSR) in HASMCs. Vitamin D receptors (VDRs) and CYP27B1 were studied in both cell types. In cultured PBMCs isolated from CKD subjects, the percentage of T helper 1(TH1) cells significantly decreased while that of T helper 2 (TH2) cells increased after cholecalciferol treatment. No significant change in intracellular and surface markers of T helper 17 (TH17) and T regulatory (Treg) cells was observed. In vitro treatment of HASMCs and HAECs with cholecalciferol led to significant and favorable alterations in mRNA expression of markers of vascular smooth muscle cells, i.e., , , and . Regarding endothelial cell markers, mRNA encoding , , , , , and were also significantly changed. Finally, the expression levels of the following proteins were notably altered: NADPH oxidase and protein kinase B (Akt) (in HAECs); SM-MHC and SM-Calponin (in HASMCs). In vitro treatment of PBMCs with cholecalciferol led to a favorable change in T-cell population, decreasing TH1 and increasing TH2 cell percentage, along with beneficial alterations in mRNA expression of HASMCs and HAECs' cell markers. This study provides evidence that cholecalciferol can influence immune and vascular function in CKD.
维生素D已被证明可改善免疫力以及血管功能。我们研究了胆钙化醇对20名维生素D缺乏的非糖尿病慢性肾脏病（CKD）患者外周血单个核细胞（PBMC）中T细胞表型的影响。我们还分别研究了维生素D对人主动脉内皮细胞（HAEC）和人主动脉平滑肌细胞（HASMC）中内皮和血管功能标志物的影响。我们在HAEC中研究了内皮型一氧化氮合酶（eNOS）、丝裂原活化蛋白激酶38（p38丝裂原活化蛋白激酶）、蛋白激酶B（Akt）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶），在HASMC中研究了α平滑肌肌动蛋白（α-SMA）、平滑肌钙调蛋白（SM-钙调蛋白）、平滑肌肌球蛋白重链（SM-MHC）和钙敏感受体（CaSR）。在两种细胞类型中均研究了维生素D受体（VDR）和CYP27B1。在从CKD患者分离的培养PBMC中，胆钙化醇处理后辅助性T细胞1（TH1）细胞百分比显著降低，而辅助性T细胞2（TH2）细胞百分比增加。未观察到辅助性T细胞17（TH17）和调节性T（Treg）细胞的细胞内和表面标志物有显著变化。用胆钙化醇对HASMC和HAEC进行体外处理导致血管平滑肌细胞标志物的mRNA表达发生显著且有利的改变，即 、 和 。关于内皮细胞标志物，编码 、 、 、 、 和 的mRNA也有显著变化。最后，以下蛋白质的表达水平发生了显著改变：NADPH氧化酶和蛋白激酶B（Akt）（在HAEC中）；SM-MHC和SM-钙调蛋白（在HASMC中）。用胆钙化醇对PBMC进行体外处理导致T细胞群体发生有利变化，降低TH1细胞百分比并增加TH2细胞百分比，同时HASMC和HAEC细胞标志物的mRNA表达也发生有益改变。这项研究提供了证据表明胆钙化醇可影响CKD患者的免疫和血管功能。
