# High Glucose-Induced Alterations in Regucalcin Expression in Podocytes and Their Potential Consequences

## TL;DR

This study shows that high glucose levels disrupt RGN expression in podocytes, which may contribute to diabetic kidney disease by affecting calcium balance.

## Contribution

The study is the first to demonstrate RGN expression and its dysregulation in podocytes under high-glucose conditions.

## Key findings

- RGN is expressed in podocytes and is dysregulated at both mRNA and protein levels under high-glucose conditions.
- RGN localizes to the endoplasmic reticulum and associates with SERCA, a key calcium-handling enzyme.
- Altered RGN expression in podocytes may contribute to diabetic kidney disease progression via calcium homeostasis disruption.

## Abstract

Regucalcin (RGN) is a multifunctional regulator of intracellular calcium signaling, implicated in cellular homeostasis and stress responses. While aberrant RGN activity has been associated with diabetic kidney disease (DKD), existing studies have primarily focused on its role in proximal tubular cells. Whether RGN is expressed in podocytes and how its expression responds to diabetic-like stimuli remain largely unexplored. Podocyte injury under diabetic conditions is a critical event in DKD pathogenesis. Therefore, in this study, we aimed to investigate whether podocytes express RGN and how its expression is affected under high-glucose (HG) conditions. To address these questions, we employed quantitative real-time PCR, Western blotting, fluorescence-based protein staining, and immunohistochemical analysis of renal sections. Our results confirmed RGN expression in podocytes and revealed its dysregulation at both the mRNA and protein levels under HG conditions. Additionally, we identified the subcellular localization of RGN and a significant association with sarco/endoplasmic reticulum calcium ATPase (SERCA), a key enzyme regulating endoplasmic reticulum (ER) calcium storage and the ER stress response. Altered RGN expression in podocytes exposed to HG concentrations may contribute to the progression of DKD, possibly through the disruption of intracellular calcium homeostasis.