缺氧环境下HIF-1调控PAD4介导的H3cit促进子宫内膜腺上皮细胞凋亡

doi:10.3969/j.issn.1006-6233.2023.09.05

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Abstract Objective: To investigate the effects of HIF-1 and PAD4 on apoptosis of endometrial epithelial cells under hypoxia and its related mechanisms. Methods: Endometrial glandular epithelial cells CM-H058 were cultured under normal and anoxic conditions, and the expressions of HIF-1, PAD4, H3cit, Caspase3 and Caspase7 were detected by qRT-PCR and Western blot. The apoptosis level of cells was detected by flow cytometry. sh-NC, sh-HIF-1, oe-NC and oe-PAD4 were transfected into CM-H058 by lentivirus transfection method, then cultured in anoxic environment and divided into sh-NC group, sh-HIF-1 group, sh-HIF-1+oe-NC group, and sh-HIF-1+ oe-PAD4 group. The expressions of HIF-1, PAD4, H3cit, Caspase3, Caspase7 and apoptosis of cells in each group were detected. The concentration of PAD4, H3cit, and H3K27ac in TSS of Caspase3 and Caspase7 were detected. Results: Compared with the normal oxygen group, the expressions of HIF-1, PAD4, H3cit, Caspase3 and Caspase7 in the hypoxia group were increased (P<0.05), and the apoptosis level was increased (P<0.05). Compared with the sh-NC group, the expressions of HIF-1, PAD4, H3cit, Caspase3 and Caspase7 in sh-HIF-1 group were decreased (P<0.05), and the apoptosis level was decreased (P<0.05). Compared with sh-HIF-1+oe-NC group, the expressions of PAD4, H3cit, Caspase3, and Caspase7 in sh-HIF-1+oe-PAD4 group were increased (P<0.05), and the apoptosis level was increased (P<0.05), and the enrichment level of PAD4, H3cit and H3K27ac in TSS of Caspase3, and Caspase7 were increased (P<0.05). Conclusion: HIF-1 promotes PAD4 expression. PAD4 and its catalyzed H3cit further enriched Caspase3 and Caspase7 TSS, promoted the transcription and expression of Caspase3 and Caspase7, and finally induced apoptosis of endometrial epithelial cells.

Key words： Anoxic environment Anoxic-inducing factor 1 Arginine deiminase 4 Endometrial gland epithelial cells Apoptosis

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	HUANG Yong
	LUO Shu
	LIAO Yuan
	et al

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HUANG Yong,LUO Shu,LIAO Yuan, et al. HIF-1 Regulates PAD4-Mediated H3cit and Promotes Apoptosis of Endometrial Glandular Epithelial Cells under Hypoxia[J]. HeBei Med, 2023, 29(9): 1432-1437.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.09.05 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I9/1432

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