What does this research mean for the field?

Gallic acid attenuates the progression of IgA nephropathy by inhibiting oxidative stress and ferroptosis through the DUSP1/p38 MAPK signaling axis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study investigates how gallic acid exerts protective effects against IgA nephropathy by affecting specific molecular pathways.

March 14, 2026Biocell0 citationsOpen Access

Research on the Mechanism of Gallic Acid Inhibiting Ferroptosis and Delaying IgA Nephropathy by Regulating the MAPK Signaling Pathway through DUSP1

QWQ WangXinjiang Medical University QWQin WangXinjiang Medical University WYWen YeXinjiang Medical University

Key Points

This study investigates how gallic acid exerts protective effects against IgA nephropathy by affecting specific molecular pathways.
Combined transcriptomics and network pharmacology to identify differentially expressed genes (DEGs).
Utilized bioinformatic tools to forecast gallic acid's targets and conduct functional enrichment analysis.
Created an IgA nephropathy model in vitro using human mesangial cells stimulated with polymeric IgA1.
Evaluated oxidative stress markers and core protein expressions using Western blot analysis.
Identified 1141 DEGs in IgAN with MAPK signaling as the most enriched pathway.
Found DUSP1 as the most downregulated gene from the intersecting targets of gallic acid and DEGs.
GA treatment significantly reduced oxidative stress and ferroptosis in HMCs.
GA increased DUSP1 expression, leading to reduced p38 MAPK phosphorylation and higher GPX4 and SLC7A11 levels.

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), Fe2+, 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.

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Cite This Study

Wang et al. (Thu,) studied this question.

synapsesocial.com/papers/69b4fb1bb39f7826a300b9fc https://doi.org/https://doi.org/10.32604/biocell.2026.075633

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