Effect of m6A demethylase ALKBH5 on proliferation and migration of cardiac fibroblasts induced by high glucose
- VernacularTitle:m6 A去甲基化酶ALKBH5对高糖诱导心肌成纤维细胞增殖与迁移能力的影响
- Author:
Zhi-yan LIU
1
;
Li-chan LIN
;
Zhen-yu LIU
;
Ji-ming SHA
;
Peng LIU
;
Sui MAO
;
Yun-sen ZHANG
;
Rui LI
;
Ye ZHANG
;
Hui TAO
Author Information
- Publication Type:Journal Article
- Keywords: RNA methylation; ALKBH5; cardiac fi-broblasts; proliferation; migration; myocardial fibrosis
- From: Chinese Pharmacological Bulletin 2025;41(2):235-241
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of N6-methy-ladenosine(m6A)demethylase ALKBH5 on the prolif-eration and migration of cardiac fibroblasts(CFs)in-duced by high glucose.Methods Primary CFs were isolated from neonatal mouse hearts and identified u-sing optical and confocal microscopy.Cell activation was induced using a high-glucose medium(33 mmol·L-1 glucose).An ALKBH5 overexpression model was established by transfecting CFs with an ALKBH5 ex-pression vector in a high-glucose medium.The expres-sion of ALKBH5 in CFs was assessed through immuno-fluorescence staining,Western blot and RT-qPCR.Changes in m6A levels were evaluated using Dot blot a-nalysis.Additionally,Alterations in the expression of proliferating cell nuclear antigen(PCNA)and collagenⅠ,a pivotal fibrosis indicator,were measured using Western blot.The proliferation and migration ability of CFs were assessed through EdU staining and Transwell migration assay,respectively.Results Following treatment with high glucose,the expression of ALKBH5 in CFs notably decreased,while m6A level increased.This was accompanied by a significant increase in the expression of the proliferation marker PCNA and the fi-brosis marker collagen Ⅰ.Additionally,there was a sig-nificant improvement in the ability of proliferation and migration.Overexpression of ALKBH5 resulted in a significant decrease in the expressions of PCNA and collagen Ⅰ,leading to the inhibition of both proliferation and migration in CFs.Conclusion Overexpression of ALKBH5 suppresses the expression of PCNA and colla-gen Ⅰ,consequently reducing the proliferation and mi-gration of CFs,potentially through m6A methylation modification.
