Diethyl citrate inhibits vascular calcification in chronic kidney disease by CaSR/autophagy signaling axis / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the effects of calcium sensitive receptor (CaSR)/autophagy signaling axis on the inhibition of vascular calcification in chronic kidney disease (CKD) by diethyl citrate (Et2Cit). Methods: Rats and vascular smooth muscle cells (VSMCs) were divided into 5 groups normal control group, model group, low-dose Et2Cit group, high-dose Et2Cit group and high-dose Et2Cit+NPS-2143 (CaSR inhibitor) group. After the intervention, the content of aorta calcium in each group was detected. Alizarin red staining was used to detect calcification in each cell group. mRNA expressions of calcification-related proteins, CaSR and autophagy-related proteins in the aorta of each group were detected by qRT-PCR. The expressions of the above proteins in each group were detected by Western blotting. Results: Compared with the control group, the calcification in model group was significantly increased, and Et2Cit intervention could reduce the calcification in a dose-dependent manner (P<0.05). Compared with high-dose Et2Cit group, high-dose Et2Cit+NPS-2143 group had significantly higher calcium content (P<0.05). Compared with those in the control group, the expressions of smooth muscle 22α (SM22α), CaSR and Beclin1 were decreased (P<0.05), while the expressions of runt related transcription factor 2 (RUNX2) and P62 were increased (P<0.05). Et2Cit intervention could reverse the above changes (P<0.05). Compared with the high-dose Et2Cit group, the high-dose Et2Cit + NPS-2143 group had significantly lower SM22α, CaSR and Beclin1, and significantly higher RUNX2 and P62 levels (P<0.05). Results: Et2Cit inhibits CKD vascular calcification partly via the CaSR and CaSR/autophagy signal axis.