Expression of urinary exosomal miRNA-615-3p and miRNA-3147 in diabetic kidney disease and their association with inflammation and fibrosis

Abstract

Background

Diabetic kidney disease (DKD) is one of the most common chronic complications of type 2 diabetes mellitus (T2DM), and it is particularly important to identify a high-quality method for evaluating disease progression. Urinary exosomes contain microRNA that might promise early diagnostic and monitoring markers of DKD. The present study aimed to identify novel exosome-related markers associated with inflammation and fibrosis to assess the progression of DKD.

Method

Exosomes were extracted from the urine of 83 participants to determine the expression levels of miRNA-615-3p and miRNA-3147 in 20 healthy people, 21 patients with T2DM and 42 patients with DKD, as determined by RT-qPCR. The circulating expression level of TGF-β1 was detected by ELISA. Serum Cystatin C was measured by a latex-enhanced immunoturbidimetric method. The correlation analyses were performed for all clinical and laboratory parameters.

Result

The expression level of urinary exosomal miRNA-615-3p in DKD patients was significantly higher than that in the control group and the T2DM group by RT-qPCR. The expression of miRNA-3147 showed an upward trend in the three groups of subjects, but it was not statistically significant. The urinary exosomal miRNA-615-3p was positively correlated with serum Cystatin C, plasma TGF-β1, creatinine, BUN, PCR and 24-h urine protein, and negatively correlated with eGFR and albumin. The diagnostic efficacy of urinary exosomal miRNA-615-3p combined with the ACR was higher than that of ACR alone.

Conclusions

Urinary exosomal miRNA-615-3p may be used as a novel biomarker for evaluating the progression of DKD, and may be involved in the process of inflammation and fibrosis in DKD. The combined diagnosis of urinary exosomal miRNA-615-3p and ACR may be used as more stable and sensitive diagnostic criteria for DKD.

Keywords:

• Exosomes
• microRNA
• diabetic kidney disease
• inflammation and fibrosis

Acknowledgement

The authors would like to express their gratitude to EditSprings (https://www.editsprings.cn/) for the expert linguistic services provided.

Ethics statement

This study protocol was reviewed and approved by Medical Ethics Committee of the First Affiliated Hospital of Soochow University, approval number (2020) 196.

Consent to participate statement

Written informed consent has been obtained from participants for this study to participate in the study.

Author contributions

JW, YT and LZ conceived and designed the experiments; JW, YT, FZ and TL performed the experiments; JW, XS and LZ analyzed the data; JW, YT, XS, FZ, TL and LZ contributed reagents/materials/analysis tools; XS and LZ contributed to the writing of the manuscript. All authors read and approved the final manuscript.

Disclosure statement

The authors have no conflicts of interest to declare.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by National Natural Science Foundation of China [81600565 and 81700129], the Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars [BK20190052], Translational Research Grant of NCRCH [2020WSA01], KJXW Scientifc Grant from Suzhou Commission of Health for Young Scholars [KJXW2020002], the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Suzhou Medical and Health Innovation Project [SKY2022042].