Research on the Mechanism of Gallic Acid Inhibiting Ferroptosis and Delaying IgA Nephropathy by Regulating the MAPK Signaling Pathway through DUSP1
Qiguo Wang1, Qin Wang2, Wen Ye3, Qin Feng3, Ting Wang3,*
1
Department of Critical Care Medicine, Xinjiang Uygur Autonomous Region Institute of Traditional Chinese Medicine,Urumqi, China
2
Department of Geriatrics, TTe Second Afffliated Hospital of Xinjiang Medical University, Urumqi, China
3
Department of Nephrology, TTe Second Afffliated Hospital of Xinjiang Medical University, Urumqi, China
* Corresponding Author: Ting Wang. Email: cherry810131@163.com
* Corresponding Author: Ting Wang. Email: 
(This article belongs to the Special Issue: Bioactive Natural Components as Regulators of Cellular Pathways and Disease Progression)
BIOCELL https://doi.org/10.32604/biocell.2026.075633
Received 05 November 2025; Accepted 14 January 2026; Published online 11 March 2026
Abstract
Objectives: IgA nephropathy (IgAN) is a common primary glomerulonephritis with limited treatment options. Gallic acid (GA) has demonstrated renal protective effects, but its precise mechanisms against IgAN remain incompletely elucidated. This study aims to reveal the molecular mechanism by which GA exerts a renal protective effect on IgAN.
Methods: Transcriptomics and network pharmacology were combined in an integrative manner. The GSE175759 dataset’s differentially expressed genes (DEGs) were filtered out. SwissTargetPrediction and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were used to forecast GA’s goals. Core targets and pathways were obtained by functional enrichment analysis. Human mesangial cells (HMCs) were stimulated with polymeric IgA1 (p-IgA1) to create an IgAN model
in vitro. Reactive oxygen species (ROS), glutathione/glutathione oxidized (GSH/GSSG), lipid peroxidation, malondialdehyde (MDA), Fe
2+, and mitochondrial membrane potential levels were evaluated in relation to GA. Western blot analysis was used in conjunction with gain-of-function (overexpression) and loss-of-function (siRNA) assays to examine the expression of the core protein and the downstream target proteins.
Results: Bioinformatic analysis identified 1141 DEGs in IgAN, with mitogen-activated protein kinase (MAPK) signaling being the most significantly enriched pathway. Intersection of 109 GA predicted targets with DEGs yielded 8 candidate genes, including dual-specificity phosphatase 1 (DUSP1), which was the most downregulated gene.
In vitro, GA treatment significantly alleviated p-IgA1-induced oxidative stress and ferroptosis in HMCs. These protective effects were dependent on DUSP1. Mechanistically, GA upregulated DUSP1 expression, thereby inhibiting p38 MAPK phosphorylation and subsequently increasing the protein levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11).
Conclusion: This study demonstrates that GA may attenuate IgAN progression by inhibiting oxidative stress and ferroptosis in HMCs via the DUSP1/p38 MAPK signaling axis.
Keywords
Gallic acid; IgA nephropathy; dual-specificity phosphatase 1 (DUSP1); p38 mitogen-activated protein kinase (p38 MAPK) pathway; ferroptosis; oxidative stress
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