Wei Tangwen, Qin Yang, Lin Xiaohui, Wang Xiujuan, Chen Suyi, Chen Xia, Yan Nan, Wei Xinyi, Zhang Zhichang, Wei Bing
Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, Guangxi, China.
Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
Front Physiol. 2025 Apr 10;16:1516466. doi: 10.3389/fphys.2025.1516466. eCollection 2025.
Diabetic nephropathy (DN), a leading cause of end-stage renal disease, exerts a substantial burden on healthcare systems globally. Emerging evidence highlights ferroptosis - an iron-dependent form of cell death driven by lipid peroxidation and glutathione depletion - as a critical contributor to DN progression via oxidative stress, tubular injury, and glomerular dysfunction. Despite increasing research interest, a comprehensive synthesis of research trends and mechanistic insights is lacking.
This study integrated bibliometric analysis with a mechanistic review to map the evolving ferroptosis landscape in DN, identify research hotspots, and propose future directions for therapeutic development.
In total, 86 publications (2018-2023) were retrieved from the Web of Science Core Collection and analyzed using CiteSpace and VOSviewer. Co-occurrence networks, citation trends, and keyword bursts were examined to delineate global contributions, collaborative networks, and emerging themes.
Annual publication numbers surged 12-fold after 2020, with China contributing the highest proportion (60.4%), and led by institutions such as Zhengzhou University. The United States of America and Germany showed high centrality in collaborative networks. Key research themes included glutathione peroxidase 4 (GPX4)-mediated antioxidant defenses, acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated lipid remodeling, and iron dysregulation. (nine articles) and (highest citation count: 171) emerged as pivotal publication platforms. Mechanistic analyses identified three ferroptosis defense axes (GPX4, FSP1/CoQ10, and GCH1/BH4) and cell type-specific vulnerabilities in tubular, podocyte, and endothelial cells. Preclinical agents, including ginkgolide B (GB) and dapagliflozin, effectively restored iron homeostasis and attenuated oxidative damage.
Ferroptosis is a promising therapeutic target for DN, yet its clinical translation remains in its infancy. Future efforts should prioritize large-scale clinical trials, single-cell mechanistic profiling, and interdisciplinary integration to bridge molecular insights with precision therapies. This study provides a roadmap for advancing ferroptosis-targeted interventions for DN, emphasizing global collaborations and biomarker-driven strategies.
糖尿病肾病（DN）是终末期肾病的主要病因，给全球医疗系统带来了沉重负担。新出现的证据表明，铁死亡——一种由脂质过氧化和谷胱甘肽耗竭驱动的铁依赖性细胞死亡形式——是通过氧化应激、肾小管损伤和肾小球功能障碍导致DN进展的关键因素。尽管研究兴趣日益浓厚，但缺乏对研究趋势和机制见解的全面综合。
本研究将文献计量分析与机制综述相结合，以描绘DN中铁死亡格局的演变，确定研究热点，并为治疗开发提出未来方向。
总共从科学引文索引核心合集检索了86篇出版物（2018 - 2023年），并使用CiteSpace和VOSviewer进行分析。研究共现网络、引文趋势和关键词爆发情况，以描绘全球贡献、合作网络和新兴主题。
2020年后年度出版物数量激增12倍，中国贡献比例最高（60.4%），以郑州大学等机构为首。美国和德国在合作网络中具有较高的中心性。关键研究主题包括谷胱甘肽过氧化物酶4（GPX4）介导的抗氧化防御、酰基辅酶A合成酶长链家族成员4（ACSL4）介导的脂质重塑和铁失调。《细胞死亡与疾病》（9篇文章）和《自由基生物学与医学》（最高被引次数：171次）成为关键的出版平台。机制分析确定了三个铁死亡防御轴（GPX4、FSP1/CoQ10和GCH1/BH4）以及肾小管、足细胞和内皮细胞中细胞类型特异性的脆弱性。临床前药物，包括银杏内酯B（GB）和达格列净，有效恢复了铁稳态并减轻了氧化损伤。
铁死亡是DN一个有前景的治疗靶点，但其临床转化仍处于起步阶段。未来的工作应优先开展大规模临床试验、单细胞机制分析以及跨学科整合，以将分子见解与精准治疗联系起来。本研究为推进针对DN的铁死亡靶向干预提供了路线图，强调全球合作和生物标志物驱动的策略。
