Protective Role of Vitamin D Receptor Against Mitochondrial Calcium Overload from PM-Induced Injury in Renal Tubular Cells

Overview

Journal Redox Biol

Date 2025 Feb 1

PMID 39891958

Authors

Mengqiu Lu

Zishun Zhan

Dan Li

Hengbing Chen

Aimei Li

Jing Hu

Zhijun Huang

Bin Yi

Affiliations

Soon will be listed here.

Abstract

Purpose: This research explores the consequences of being exposed to PM contribute to renal injury while also evaluating the protective role of Vitamin D-VDR signaling in alleviating mitochondrial calcium imbalance and oxidative stress in renal tubular cells.

Methods: Animal models of chronic PM exposure were used to simulate environmental conditions in wild type and VDR-overexpressing mice specific to renal tubules. In parallel, HK-2 cell lines were treated with PM in vitro. Mitochondrial function, calcium concentration, and oxidative stress markers were assessed. VDR activation, achieved through genetic overexpression and paricalcitol, was induced to examine its effect on mitochondrial calcium uniporter (MCU) expression and mitochondrial calcium regulation.

Results: PM exposure caused significant mitochondrial damage in renal tubular cells, including mitochondrial calcium overload, increased oxidative stress, reduced membrane potential, and diminished ATP production. Elevated MCU expressions were a key contributor to these disruptions. VDR activation effectively reversed these effects by downregulating MCU, restoring mitochondrial calcium balance, reducing oxidative stress, and improving renal function.

Conclusion: This study shows that activating Vitamin D-VDR signaling shields the kidneys from PM-induced damage by reestablishing mitochondrial calcium balance and lowering oxidative stress via inhibition of the MCU. These results unveil a new protective role of VDR in defending against environmental pollutants and suggest that targeting the MCU could offer a potential therapeutic strategy for treating chronic kidney disease linked to pollution exposure.

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