Role and mechanism of RASAL1 in increase of pulmonary vascular endothelial permeability induced by homocysteine
10.12360/CPB202312060
- VernacularTitle:RASAL1在同型半胱氨酸致肺血管内皮通透性增加中的作用及机制研究
- Author:
Xin-Yi LI
1
;
Kai-Yue QIN
;
Zi-Yao YANG
;
Ling ZHANG
;
Zhen LI
;
Ya-Li YANG
;
Xi XU
;
Xiao-Ling YANG
Author Information
1. 国家卫健委代谢性心血管疾病研究重点实验室
- Keywords:
homocysteine;
RASAL1;
pulmonary mi-crovascular endothelial cells;
permeability;
DNA methylation;
DNMT1
- From:
Chinese Pharmacological Bulletin
2024;40(8):1454-1461
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of homocys-teine(Hcy)on the permeability of pulmonary micro-vascular endothelial cells(PMVECs)and the role and mechanism of RASAL1.Methods CBS+/-mice were fed a high methionine diet(HMD)for 16 weeks to replicate an animal model of hyperhomocysteinemia(HHcy).HE staining was used to observe the changes in lung tissue structure.qRT-PCR was used to detect the levels of RASAL1 and DNMT1 mRNA in lung tis-sue.Western blot was used to detect the expression of RASAL1,DNMT1,ZO-1,and VE cadherin proteins.Methylation specific PCR was used to detect methyla-tion in the RASAL1 promoter region.PMVECs were transfected with Ad-RASAL1 to detect the expression of ZO-1 and VE cadherin.The si-DNMT1 interference fragment was transfected into PMVECs,and the ex-pression of the RASAL1 was detected by qRT-PCR and Western blot.Results Serum Hcy level of HMD mice was significantly raised,and HE staining showed severe structural disorder in lung tissue.The expres-sion of RASAL1,ZO-1,and VE cadherin was de-creased,while the expression of DNMT1 was in-creased.The degree of methylation in the RASAL1 promoter region was raised.The expression of ZO-1 and VE cadherin increased after PMVECs were trans-fected with Ad-RASAL1.After knocking down DN-MT1,RASAL1 expression was increased.Conclusion Hcy can increase the permeability of PMVECs,and its mechanism is related to the upregulation of RASAL1 methylation level.
