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Autophagy-dependent ferroptosis is involved in the development of endometriosis

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posted on 2023-08-08, 23:20 authored by Hui Li, Huadi Yang, Shenyi Lu, Xinyan Wang, Xinhe Shi, Peiyu Mao

Endometriosis (EMS) is an estrogen-dependent condition with unclear pathogenesis. Recent findings suggest implicate autophagy and ferroptosis in EMS development.

We assessed autophagy and ferroptosis proteins in EMS patients using immunohistochemistry and western blot and established an EMS rat model through allograft endometrial transplantation, confirmed via hematoxylin and eosin staining and epithelial–mesenchymal transition -related proteins. Primary EMS cells were isolated from the model rats and cultured under five conditions: control, EMS, EMS with Rapamycin (autophagy inducer), EMS with si-Atg5 (autophagy inhibitor), and EMS with si-Atg5 plus Erastin (ferroptosis inducer). We evaluated cell viability, iron content, oxidative stress, and mitochondrial morphologyin EMS cells, and detected autophagy and ferroptosis proteins through immunofluorescence, western blot, and monodansylcadaverine staining.

Autophagy proteins Beclin1 and LC3 were highly expressed, whereas p62, glutathione peroxidase 4, and p53 were lowly expressed in EMS patients. Rapamycin decreased cell viability but increased iron content, reactive oxygen species, lipid peroxide production, the number of ferroptotic mitochondria, and the expression of autophagy proteins in EMS cells, while si-Atg5 showed opposite effects. Additionally, Erastin reversed the impact of si-Atg5 on EMS cells.

Our findings suggest that autophagy-dependent ferroptosis plays a role in EMS progression.

Funding

This work was supported by the National Natural Science Foundation of China under Grant No. 82104909, Traditional Chinese Medicine Administration Project of Zhejiang Province, China under Grant No. 2023ZL036, Health Commission Project of Zhejiang Province, China under Grant No. 2020KY664, and Project of Zhejiang Chinese Medical University, China under Grant No. 2022JKZKTS41.

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