{"paper_id":"340c8f34-6840-456b-b480-bdd1da1e0c0f","body_text":"Abstract\nAims\nCurrent evidence suggests that there is no completely effective method for endometriosis (EMS) without trauma due to diverse adverse effects. Reliable evidence illustrates that inhibiting ferroptosis is a potential strategy for EMS. We sufficiently verified that the expression of endogenous protein PDZ and LIM domain 3 (PDLIM3) was significantly increased in EMS.\nMethods\nPDLIM3 knockdown reduced primary ectopic endometrial stromal cells’ (EESCs) viability and migration, and elevated ferroptosis signaling indicators including Fe2+, malondialdehyde (MDA), and reactive oxygen species (ROS) in EESCs.\nResults\nMechanistic studies revealed that inhibition of PDLIM3 accelerated glioma-associated oncogene-1 (Gli1) degradation and further deactivated Hedgehog signaling. Gli1 inhibitor, GANT61, abrogated the impact of PDLIM3 deletion on EESC growth, migration, and ferroptosis. In vivo experiments suggested that PDLIM3 reduction repressed the growth of endometrial lesions. Likewise, repression of PDLIM3 promoted ferroptosis and attenuated Hedgehog signaling in endometrial lesions.\nConclusions\nCollectively, silencing of PDLIM3 facilitates ferroptosis in EMS by inducing Gli1 degradation and blocking Hedgehog signaling. It may provide an alternative strategy for developing therapeutic agents of EMS in the future.\nSimilar content being viewed by others\nReferences\nBougie O, McClintock C, Pudwell J, Brogly SB, Velez MP. Long-term follow-up of endometriosis surgery in Ontario: a population-based cohort study. Am J Obstet Gynecol. 2021;225(3):270. e271-270 e219.\nSchwartz K, Llarena NC, Rehmer JM, Richards EG, Falcone T. The role of pharmacotherapy in the treatment of endometriosis across the lifespan. 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Med Res Rev. 2021;41(4):2489–564.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSupplementary information\nESM 1 (download DOCX )\nSupplementary Table 1. Primers used for qRT-PCR analysis\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nLiu, M., Wang, X. & Zhu, J. PDLIM3 knockdown promotes ferroptosis in endometriosis progression via inducing Gli1 degradation and blocking Hedgehog signaling pathway. J Assist Reprod Genet 41, 2117–2128 (2024). https://doi.org/10.1007/s10815-024-03131-8\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s10815-024-03131-8","source_license":"CC0","license_restricted":false}