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  3. Excess iron accumulation mediated senescence in diabetic kidney injury

Excess iron accumulation mediated senescence in diabetic kidney injury

  • J Biochem Mol Toxicol. 2024 Apr;38(4):e23683. doi: 10.1002/jbt.23683.
Xueer Cheng 1 2 3 4,  Yanyan Li 5,  Li Chen 1 2 3 4,  Chunjie Jiang 1 2 3 4,  Shufen Peng 6,  Ping Yao 1 2 3 4,  Yuhan Tang 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Hygiene, Key Laboratory of Environment & Health, Ministry of Education, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Nutrition and Food Hygiene, State Environment of Protection Key Laboratory of Health Effects of Environmental Pollution, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Nutrition and Food Hygiene, State Key Laboratory of Environment Health (Incubation), Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Department of Teaching and Research, Shenzhen Center for Chronic Disease Control, Shenzhen, China.
  • 6 Department of Nutrition, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
PMID: 38483099 DOI: 10.1002/jbt.23683
Abstract

Cellular senescence and iron accumulation were separately observed in diabetic nephropathy (DN). Limited evidence supports that iron was significantly accumulated in senescent cells. We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN. Renal cells were treated with high glucose (HG, 35 mM) for 10 or 15 days, and DN mice were induced by high-fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, β-galactosidase staining, 5-ethynyl-2-deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN. Lactate Dehydrogenase (LDH) release was increased by HG and reversed by p16/p21 knockdown, and the supernatant of HG-treated cells caused increased LDH release from normal cells. Iron metabolism-related protein expression was disordered after HG exposure concomitant with senescence. Ferric ammonium citrate (50 μM) upregulated gamma-H2A.X variant histone and increased the senescence markers in HG-treated cells. The treatment of deferoxamine (0.5 μM) had the opposite effect. Compared to the non-DN individual, increased ferritin and senescence markers were verified in DN mice and patients, and the co-localization of ferritin and senescence markers was observed by immunofluorescence. These results suggested that accumulated iron was correlated with aggravated DNA damage and accelerated senescence, and revealed the role of iron in the cellular senescence of diseases.

Keywords

HBZY-1; HK-2; diabetic nephropathy; ferritin; iron accumulation; senescence.

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