IL-37 inhibits osteogenic transformation of human aortic vascular smooth muscle cells and participates in inhibition of their calcification via TLR/NF-κB pathway
10.3969/j.issn.1000-484X.2025.02.008
- VernacularTitle:IL-37通过调控NF-κB通路抑制人主动脉血管平滑肌细胞成骨转化并参与抑制其钙化
- Author:
Chenyue MA
1
;
Qiongyi HE
;
Meng WANG
;
Meng CHAI
;
Haitao ZHANG
Author Information
1. 安徽医科大学空军临床学院,安徽医科大学第五临床学院,合肥 230032;空军特色医学中心心内科,北京 100142
- Publication Type:Journal Article
- Keywords:
IL-37;
Human aortic vascular smooth muscle cells;
Osteogenic transformation;
TLR/NF-κB pathway
- From:
Chinese Journal of Immunology
2025;41(2):304-309
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of IL-37 on oxidized low-density lipoprotein(ox-LDL)-induced calcification in human aortic vascular smooth muscle cells(HA-SMCs)and the influence of toll-like receptor(TLR)/nuclear transcription factor(NF-κB)pathway and osteogenic transcription factors,to demonstrate the mechanism of IL-37 in calcification.Methods:The calcifica-tion model of HA-SMCs was treated with ox-LDL,and the model group was pretreated with 100 ng/ml IL-37 or 100 μmol/L PDTC.CCK8 was used to detect cell proliferation activity;flow cytometry was used to detect apoptosis.Alizarin red staining was used to detect calcified nodules.The mRNA levels of smooth muscle actin(SMA),bone morphogenetic protein(BMP2)and IL-37 were detected by qPCR;mRNA and protein expression levels of TLR,NF-κB,p-NF-κB,RUNX-associated transcription factor(RUNX2),alkaline phosphatase(ALP),SMA and smooth muscle 22α(SM22α)were detected by qPCR and Western blot.Results:Compared with the control group,ox-LDL treatment enhanced cellular proliferation activity and was concentration-dependent(P<0.05),and apoptosis rate was increased,while the model group produced significant orange-red calcified nodules,up-regulated mRNA and protein expres-sion of inflammatory factors such as TLR and NF-κB,up-regulated mRNA expression of IL-37,RUNX2,BMP2,ALP,while SMA and SM22α mRNA expressions were decreased,and the protein expressions of p-NF-κB and RUNX2 were increased significantly;compared with the modeling group,the IL-37 pretreatment group showed lower viability and decreased apoptosis rate(P<0.05),sig-nificantly reduced calcified nodules,and the mRNA and protein expression of inflammatory factors such as TLR and NF-κB,and mRNA of RUNX2,BMP2,ALP expressions were downregulated,mRNA expression of SMA and SM22α were elevated,and protein expressions of p-NF-κB and RUNX2 were significantly decreased,showing the same trend as the inhibitor PDTC group in cytokines.Conclusion:IL-37 inhibits calcification of HA-SMCs,which may be related to the inhibition of NF-κB pathway and osteogenic pheno-type transformation.
