Interaction of circulating TGFβ regulatory miRNAs in different severity of diabetic kidney disease

Abstract

Aims

To explore the interaction of TGFβ regulatory microRNAs (miRNAs) with different severities of diabetic kidney disease (DKD).

Methods

According to different UACR (30 and 300 mg/g), 436 subjects were included, and high glucose induced RMCs were cultured. Real-time PCR, ELISA, and automatic biochemical analysis were used to measure miRNAs, TGFβ1, and other biochemical indicators in serum and RMCs. Target genes of miRNA were predicted and visualised by bioinformatics.

Results

HbA1c, TGFβ1, miR-217, and miR-224 in T2DM patients increased with UACR, while miR-192 and miR-216a decreased. Ln UACR was positively correlated with HbA1c, TGFβ1, miR-217, and miR-224, and negatively correlated with miR-192 and miR-216a. High glucose and TGFβ1 affected miRNAs and these miRNAs affected each other. The miRNA target genes mainly revolve around PTEN, PI3K/Akt, and MAPK signalling pathways.

Conclusion

TGFβ regulatory miRNAs and different severity of DKD have a potential interaction regulating fibrosis through PTEN, PI3K/Akt, and MAPK pathways.

Keywords:

• Diabetic kidney disease
• microRNA
• transforming growth factor β
• urinary albumin excretion rate
• bioinformatics

Ethical approval

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.

Acknowledgements

This study was supported by the National Key Research and Development Program of China (Grant number: 2018YFC1313900; 2018YFC1313901), the Higher School “High-end Talent Team Construction” of Liaoning Province (Grant number: [2014]187), and the “Natural Science Foundation of Liaoning Province” (Grant number: 201602862), and the Doctoral Research Initiation Fund Project of Liaoning Province (Grant No. 2021-BS-206). This manuscript was submitted as a pre-print in the link "https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3405557.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.