Minerva Endocrinology 2022 Feb 01

DOI: 10.23736/S2724-6507.22.03646-6

Copyright © 2022 EDIZIONI MINERVA MEDICA

lingua: Inglese

A clinical and in-silico study of MicroRNA-21 and growth differentiation factor-15 expression in pre-diabetes, type 2 diabetes and diabetic nephropathy

Riddhi G. AGARWAL ¹, Manoj KHOKHAR ¹, Purvi PUROHIT ¹ ✉, Anupama MODI ¹, Nitin K. BAJPAI ², Gopal K. BOHRA ³, Mahendra K. GARG ³, Praveen SHARMA ¹

¹ Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India; ² Department of Nephrology, All India Institute of Medical Sciences, Jodhpur, India; ³ Department of General Medicine, All India Institute of Medical Sciences, Jodhpur, India

BACKGROUND: Diabetic Nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors.
METHODS: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (n=30) and patients with pre-Type-2 Diabetes mellitus (Pre-diabetes) (n=30), T2DM (n=30) and DN (n=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR.
RESULTS: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56 ±76.37), T2DM (1528.87 ±140.75) and DN patients (10-fold higher; 5507.90 ±503.88) when compared to healthy controls (567.36 ±69.99). The FCE of circulating hsa-miR-21 was 6.19 (Pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients.
CONCLUSIONS: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.

KEY WORDS: Biomarkers; Diabetic nephropathy; MicroRNA; Type 2 diabetes mellitus; Transforming growth factor-β