# The Role and Clinical Significance of miR‐484 in the Regulation of SGLT2 in Diabetic Nephropathy

## TL;DR

This study explores how miR-484 regulates SGLT2 in diabetic nephropathy, offering insights into its role in disease progression and potential for new treatments.

## Contribution

The study identifies miR-484 as a novel regulator of SGLT2 in diabetic nephropathy and suggests its potential as a biomarker and therapeutic target.

## Key findings

- miR-484 levels are lower in diabetic nephropathy patients and correlate with disease severity markers.
- miR-484 directly targets SGLT2, suppressing its expression in high-glucose conditions.
- Restoring miR-484 reduces oxidative stress and inflammation in kidney cells.

## Abstract

Diabetic nephropathy (DN), a severe complication of Type 2 diabetes mellitus (T2DM), is the primary reason of end‐stage kidney disease (ESKD) and is closely associated with an elevated cardiovascular risk. While miR‐484 has been implicated in diabetes, its specific role in DN remains to be elucidated.

To analyze miR‐484 expression in DN and its association with clinicopathological parameters, as well as to elucidate its molecular regulation of Sodium–glucose cotransporter protein 2 (SGLT2), providing evidence for the early diagnosis of DN and miR‐484/SGLT2‐targeted therapies.

Clinical data were collected from healthy controls and T2DM patients. Total RNA was extracted for real‐time PCR analysis. ROC curves, Pearson correlation, and logistic regression evaluated their clinical value. High glucose (30 mM)–treated HK‐2 cell models and transfections with miR‐484 mimics/inhibitors assessed cell proliferation, oxidative stress (MDA/SOD), inflammation (TNF‐α/IL‐6/IL‐1β) using cell counting kit‐8 (CCK‐8) and ELISA, and SGLT2 targeting via dual‐luciferase assays.

DN patients exhibited lower serum miR‐484 levels compared to controls and T2DM, negatively correlating with HbA1c and ACR, and positively correlating with eGFR. miR‐484 was an independent risk factor for DN demonstrating high diagnostic sensitivity. High glucose downregulated miR‐484 in HK‐2 cells, inducing proliferation inhibition, oxidative stress, and inflammation; all of which were reversed by miR‐484 mimics. Dual‐luciferase assays confirmed that miR‐484 directly targets the 3′UTR of SGLT2 to suppress its expression.

The miR‐484/SGLT2 axis is key to DN pathogenesis. miR‐484 serum levels reflect DN severity and serve as a potential biomarker. Targeting SGLT2 via miR‐484 offers new therapeutic strategies for DN by mitigating glucose reabsorption, oxidative stress, and inflammation.