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C/EBPα介导的ACSL4依赖性铁死亡加剧糖尿病肾病中的肾小管损伤。

C/EBPα-mediated ACSL4-dependent ferroptosis exacerbates tubular injury in diabetic kidney disease.

作者信息

Xia Ziru, Wei Zhaonan, Li Xin, Liu Yunzi, Gu Xiangchen, Tong Jianhua, Huang Siyi, Zhang Xiaoyue, Wang Weiming

机构信息

Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.

Institute of Nephrology, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

出版信息

Cell Death Discov. 2024 Oct 23;10(1):448. doi: 10.1038/s41420-024-02179-w.

DOI:10.1038/s41420-024-02179-w
PMID:39443466
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11499655/
Abstract

Diabetic kidney disease (DKD) is a prevalent and debilitating complication of diabetes characterized by progressive renal function decline and a lack of effective treatment options. Here, we investigated the role of the transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) in DKD pathogenesis. Analysis of renal biopsy samples revealed increased C/EBPα expression in patients with DKD. Using RNA sequencing and proteomics, we explored the mechanisms through which the C/EBPα contributes to DKD. Our findings demonstrated that C/EBPα exacerbated tubular injury by promoting acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. We identified that C/EBPα upregulated ACSL4 expression by binding to its transcription regulatory sequence (TRS), leading to elevated lipid peroxidation and ferroptosis. Furthermore, inhibition or genetic ablation of C/EBPα attenuated ferroptosis and mitigated tubular injury in DKD. These results highlighted the C/EBPα-ACSL4-ferroptosis pathway as a promising therapeutic target for DKD treatment.

摘要

糖尿病肾病（DKD）是糖尿病常见且使人衰弱的并发症，其特征是肾功能进行性下降且缺乏有效的治疗选择。在此，我们研究了转录因子CCAAT/增强子结合蛋白α（C/EBPα）在DKD发病机制中的作用。对肾活检样本的分析显示，DKD患者中C/EBPα表达增加。利用RNA测序和蛋白质组学，我们探究了C/EBPα促成DKD的机制。我们的研究结果表明，C/EBPα通过促进依赖于酰基辅酶A合成酶长链家族成员4（ACSL4）的铁死亡加剧肾小管损伤。我们发现C/EBPα通过与其转录调控序列（TRS）结合上调ACSL4表达，导致脂质过氧化和铁死亡增加。此外，抑制C/EBPα或对其进行基因敲除可减轻DKD中的铁死亡并缓解肾小管损伤。这些结果凸显了C/EBPα-ACSL4-铁死亡途径作为DKD治疗有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72c/11499655/56d6502a33f1/41420_2024_2179_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72c/11499655/74e6554d8fe5/41420_2024_2179_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72c/11499655/56d6502a33f1/41420_2024_2179_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72c/11499655/3fb8615442e0/41420_2024_2179_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72c/11499655/c5aa36fca2f3/41420_2024_2179_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72c/11499655/211e75d8a8a1/41420_2024_2179_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72c/11499655/c709f5d764dc/41420_2024_2179_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72c/11499655/74e6554d8fe5/41420_2024_2179_Fig8_HTML.jpg
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本文引用的文献

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Cell Death Differ. 2023 Oct;30(10):2280-2292. doi: 10.1038/s41418-023-01216-y. Epub 2023 Aug 26.
2
Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression.糖尿病肾病：治疗进展减缓支柱的最新进展。
Diabetes Care. 2023 Sep 1;46(9):1574-1586. doi: 10.2337/dci23-0030.
3
STING/ACSL4 axis-dependent ferroptosis and inflammation promote hypertension-associated chronic kidney disease.
STING/ACSL4 轴依赖性铁死亡和炎症促进高血压相关的慢性肾脏病。
Mol Ther. 2023 Oct 4;31(10):3084-3103. doi: 10.1016/j.ymthe.2023.07.026. Epub 2023 Aug 2.
4
Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism.酰基辅酶 A 合成酶 ACSL4：铁死亡和脂肪酸代谢中的必需靶点。
Chin Med J (Engl). 2023 Nov 5;136(21):2521-2537. doi: 10.1097/CM9.0000000000002533.
5
Emerging Role of Ferroptosis in Diabetic Kidney Disease: Molecular Mechanisms and Therapeutic Opportunities.铁死亡在糖尿病肾病中的新作用：分子机制和治疗机会。
Int J Biol Sci. 2023 May 11;19(9):2678-2694. doi: 10.7150/ijbs.81892. eCollection 2023.
6
TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR.TRIM5α 将 HDAC1 募集到 p50 和 Sp1 上，并促进 HIV-1 LTR 处的 H3K9 去乙酰化。
Nat Commun. 2023 Jun 8;14(1):3343. doi: 10.1038/s41467-023-39056-6.
7
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J Transl Med. 2023 Mar 29;21(1):228. doi: 10.1186/s12967-023-04069-8.
8
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9
Molecular pathways that drive diabetic kidney disease.驱动糖尿病肾病的分子通路。
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