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.
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2023, Vol. 29 
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