KLF7 reverses ox-LDL-induced ferroptosis in HMEC-1 cells through transcriptionally activating ALKBH5 to inhibit the m6A modification of ACSL4

Atherosclerosis is a chronic inflammatory vascular disease. It was confirmed that activation of ferroptosis could induce the development of AS. Meanwhile, Krüppel-like factor 7 was reported to be involved in AS. Nevertheless, the detailed function of KLF7 in ferroptosis during AS has not been not ex...

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Veröffentlicht in:Cytotechnology (Dordrecht) 2024-12, Vol.76 (6), p.653-666
Hauptverfasser: Xiong, Qinggen, Luo, Zhijian, Xie, Xiaoming, Zhou, Wei
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Sprache:eng
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Zusammenfassung:Atherosclerosis is a chronic inflammatory vascular disease. It was confirmed that activation of ferroptosis could induce the development of AS. Meanwhile, Krüppel-like factor 7 was reported to be involved in AS. Nevertheless, the detailed function of KLF7 in ferroptosis during AS has not been not explored. To mimic AS in vitro, human microvascular endothelial cells (HMEC-1) were exposed to 100 μg/mL ox-LDL. Cell viability was tested using MTT assay, and commercial kits were applied to examine the ferroptosis. Flow cytometry was applied for testing lipid ROS level. The relation between KLF7 and AlkB homolog 5 (ALKBH5) was explored using dual luciferase and ChIP assays. Furthermore, MeRIP was used to test the m6A modification level of ACSL4. KLF7 and ALKBH5 overexpression reversed ox-LDL-induced ferroptosis (characterized by up-regulated MDA, iron, Fe 2+ , lipid ROS and ACSL4, and down-regulated GSH and GPX4) in HMEC-1 cells. In addition, KLF7 transcriptionally activated ALKBH5. ALKBH5 decreased the level of ACSL4 by inhibiting the m6A modification of ACSL4. Furthermore, upregulation of KLF7 restored ox-LDL-induced ferroptosis in HMEC-1 cells via upregulating ALKBH5. KLF7 repressed ox-LDL-induced ferroptosis in HMEC-1 cells through promoting ALKBH5 mediated m6A demethylation of ACSL4. Our study might supply a new therapeutic strategy for AS treatment.
ISSN:0920-9069
1573-0778
DOI:10.1007/s10616-024-00641-2