GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis Via Targeting TLR2/AKR1C3

Overview

Journal Int J Biol Sci

Date 2025 Feb 3

PMID 39897029

Authors

Xiaobo Wang

Bingyu Wang

Jiawei Shi

Zefu Chen

Yongpei Wu

Jingmin Liu

Zhongmin Zhang

Yang Wang

Jia Dan

Xin Zheng

Affiliations

Soon will be listed here.

Abstract

This study explored the role of ferroptosis in intervertebral disc degeneration (IVDD), and identified GATA6 as a key regulator of this process. A ferroptosis-related gene risk coefficient model was constructed using differential gene expression analysis of the GSE70362 dataset. The analysis identified GATA6 as a significant factor in IVDD progression. GATA6 was shown to promote ferroptosis in nucleus pulposus cells (NPCs) by regulating the expression of AKR1C3 through the TLR2 pathway. experiments demonstrated that GATA6 knockdown reduced ferroptosis, improved cell viability, and mitigated extracellular matrix degradation, whereas GATA6 overexpression exacerbated these processes. Furthermore, AKR1C3 was found to be crucial for GATA6-mediated ferroptosis, and modulation of the TLR2-AKR1C3 axis significantly impacted the degeneration of NPCs. These findings suggest that targeting GATA6 and its downstream TLR2-AKR1C3 pathway may provide new therapeutic approaches for IVDD.

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