# Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury

## TL;DR

This study identifies redox gene dysregulation in a rat model of kidney injury linked to metabolic syndrome, with a focus on the CCL5 gene as a potential biomarker.

## Contribution

The study reveals specific downregulation of six oxidative stress-related genes in metabolic syndrome-induced kidney injury, with functional validation of CCL5.

## Key findings

- MetS rats showed systemic oxidative stress and kidney injury markers like hypertension and lipid peroxidation.
- Transcriptomic analysis identified six downregulated oxidative stress-related genes in renal tissue.
- CCL5 was confirmed to be repressed at both mRNA and protein levels in multiple compartments.

## Abstract

Metabolic syndrome (MetS), characterized by obesity, insulin resistance, and dyslipidemia, is a major risk factor for renal injury. Oxidative stress (OxS) plays a pivotal role in its progression; however, the underlying molecular mechanisms are not fully understood. In this study, we established a rat model of MetS using a high-fat diet combined with a single-dose streptozotocin injection in male Wistar rats. MetS rats exhibited systemic OxS, evidenced by elevated circulating levels of free oxygen radicals and decreased antioxidant defense capacity, as well as hypertension, renal lipid peroxidation, glomerular hyperfiltration, and renal tubular injury. Transcriptomic profiling of renal tissue revealed significant downregulation of six OxS-related genes: C-C motif chemokine ligand 5 (CCL5), glutamate-cysteine ligase catalytic subunit, glutathione peroxidase 6, recombination activating gene 2, NAD(P)H: quinone oxidoreductase 1, and selenoprotein P-1. Among these downregulated genes, CCL5 was further confirmed to be repressed at both mRNA and protein levels across intrarenal and systemic compartments. Given its documented functions in immune signaling and redox homeostasis, CCL5 downregulation may contribute to enhanced oxidative damage in MetS-associated renal injury. These findings highlight the role of redox gene dysregulation in the pathogenesis of MetS-related kidney disease and support the potential of CCL5 as a biomarker for oxidative renal injury.