AOPPs induces EMT and fibrosis by activating oxidative stress through ERK/p38 MAPK signaling pathway in endometriosis

Luo X, Xiaoqing Luo, Wen S, Sixi Wen, Zeng J, Jun-ling Zeng, Junling Zeng, Jing Liu, Liu J, Wenting Ye, Ye W, Jiangpeng Wu, Wu J, Songyu Huang, Huang S, Wuwei Xie, Xie W, Wen H, Haiping Wen, Yan Sun, Sun Y, Jing Cai, Cai J, Daidi Mo, Mo D, Qian-xia Lin, Qianxia Lin, Lin Q, Chen M, Mingwei Chen, Xia S, Siyu Xia, Yali Song, Song Y
Reproductive biology · 2024 · vol. 24(4) , pp. 100950 · doi:10.1016/j.repbio.2024.100950 · PMID:39241657 · W4402307790
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Advanced oxidation protein products (AOPPs) induce epithelial-mesenchymal transition and fibrosis in endometriosis by activating oxidative stress via the ERK/p38 MAPK signaling pathway.

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Abstract

Epithelial-mesenchymal transition (EMT) is known to play a crucial role in the development of endometriosis (EMs). However, the exact mechanisms involved in EMT regulation in EMs are not well understood. In this study, we performed comprehensive research using clinical samples, single-cell sequencing, and in vivo/in vitro models to investigate the effects of advanced oxidation protein products (AOPPs) on EMT and the underlying mechanisms in EMs. Combining bioinformatics analysis with experimental validation, our results show that AOPPs accumulate in EMs tissues, and their levels positively correlate with the expression of EMT markers in fibrotic lesions of EMs patients. Stimulation with AOPPs leads to a concentration- and time-dependent alteration of EMT markers expression in both in vitro and in vivo models. These effects are mainly mediated by the generation of reactive oxygen species and nitrite, along with the activation of the ERK and P38 signaling pathways. In chronic administration studies using normal rats, AOPPs induce EMT and enhance collagen deposition. These findings significantly contribute to our understanding of the molecular mechanisms of EMs and provide a foundation for future research and therapeutic development in this field.

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Condition tags

endometriosis

MeSH descriptors

Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products Advanced Oxidation Protein Products

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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