Expression and regulation of adenosine triphosphate binding cassette subfamily C member 4 in patients with type 2 diabetes mellitus and macrovascular disease
10.3969/j.issn.1006-6187.2025.07.006
- VernacularTitle:腺苷三磷酸结合转运蛋白C4在2型糖尿病合并大血管病变中表达和调控作用的研究
- Author:
Ying YANG
1
;
Shaomin CHEN
1
;
Shaohua XU
1
;
Songmei LIU
1
Author Information
1. 430071 武汉大学中南医院检验科
- Publication Type:Journal Article
- Keywords:
Diabetes mellitus,type 2;
Macrovascular disease;
Adenosine triphosphate binding cassette subfamily C member 4;
RNA-Seq uencing
- From:
Chinese Journal of Diabetes
2025;33(7):506-511
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression and regulatory role of adenosine triphosphate binding transporter C4(ABCC4)in patients with type 2 diabetes mellitus(T2DM)and macrovascular disease(MD).Methods A total of 137 patients with T2DM were enrolled in this study from Zhongnan Hospital of Wuhan University during March 2015 and March 2017.All the participants were divided into T2DM group(n=64)and T2DM with MD group(n=73)according to the presence or absence of MD.Another 75 healthy subjects were selected as normal control(NC)group.The general data and biochemical indicators were collected and compared among the three groups.The mRNA expression level of ABCC4 was detected by real-time fluorescence quantitative PCR(qPCR),and the correlation between each indicator and ABCC4 mRNA was analyzed.ABCC4 knockout stable HepG2 cell line was constructed and transcriptome sequencing analysis(RNA-Seq)was performed.Results BMI,FPG,TC,TG and LDL-C were higher,while HDL-C was lower in T2DM and MD groups than in NC group(P<0.05).The expression levels of SBP and ABCC4 mRNA were higher in MD group than in T2DM and NC groups(P<0.05).Spearman correlation analysis showed that the level of ABCC4 mRNA was negatively correlated with cholinesterase(r=-0.359,P<0.05)and positively correlated with lipoprotein(a)(r=0.241,P<0.05).A total of 280 differentially expressed genes were screened out by RNA-Seq in ABCC4 knockout cell lines.GO and KEGG analysis showed that these differentially expressed genes were mainly enriched in biological functions such as vesicle transport and growth factor activity.It is involved in cytokine receptor interaction,glycation products-receptor for advanced glycation end products signaling pathway of DM complications,leukocyte transendothelial migration and other pathways.Conclusions ABCC4 is elevated in patients with T2DM and macrovascular disease.ABCC4 might play a role in occurrence and development of macrovascular disease through affecting the biological function of membrane,inflammation and glycation metabolism pathways.
