Interaction of Circulating TGFβ regulatory miRNAs in Different Severity of Diabetic Kidney Disease

Abstract

Aims: To explore the interaction of TGFβ regulatory microRNAs (miRNAs) in diabetic kidney disease (DKD) with different severity by measuring the serum TGFβ regulatory miRNAs and biochemical indicators in type 2 diabetes mellitus (T2DM) patients with different urinary albumin excretion rates (UACR) and performing bioinformatics analysis. Methods: 324 T2DM patients were divided into normal albuminuria, microalbuminuria and large amount of albuminuria groups (113, 109 and 102 cases, NA, MA and LA) according to different UACR ( 300 mg/g), while the normal control group (112 cases, NC) was included. Real-time PCR, ELISA, and chemiluminescence were used to measure serum miRNAs, TGFβ1 and other biochemical indicators. Target genes of miRNA were predicted and visualized by bioinformatics. Results: Compared with NC group, HbA1c, TGFβ1, miR-217 and miR-224 in T2DM patients increased with UACR, while miR-192 and miR-216a decreased. Pearson correlation analysis indicated that miR-192 and miR-216a were negatively correlated with miR-217, miR-224, TGFβ1, HbA1c, and Ln UACR, while miR-217 and miR-224 were positively correlated with TGβ1, HbA1c, and Ln UACR. Ridge regression showed that Ln UACR was positively correlated with HbA1c, TGFβ1, miR-217, and miR-224, and negatively correlated with miR-192 and miR-216a. Bioinformatics analysis shows that the potential roles of miRNA target genes mainly revolves around PTEN, PI3K/Akt and MAPK signaling pathways. Conclusion: These findings suggested that there is a potential interaction between TGFβ regulatory miRNAs and different severity of DKD, and they may regulate the fibrosis process of DKD through PTEN, PI3K/Akt and MAPK signaling pathways. Funding Statement: This study was supported by the Higher School “High-end Talent Team Construction” of Liaoning Province (No. [2014]187), and the “Natural Science Foundation of Liaoning Province [201602862]”, Liaoning Province, P.R., China. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the medical ethics committee of the First Affiliated Hospital of China Medical University. All procedures were performed in accordance with the ethical standards as mentioned in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all participants included in the study