NLRP1 promotes pyroptosis in endometriosis through the NF-κB signaling pathway

Endometriosis is a prevalent gynecological disorder characterized by chronic inflammation. Pyroptosis, a type of programmed proinflammatory cell death, plays a crucial role in various inflammatory diseases. However, its specific mechanism in endometriosis remains unclear. This study integrated transcriptome data of patients with endometriosis from the GEO database with a pyroptosis-related gene set to identify core pyroptosis markers associated with endometriosis. Bioinformatics methods were employed to analyze the expression profiles and diagnostic values of these genes. The expression of these genes was validated in clinical specimens using qRT-PCR. The specific role of NLRP1 in endometriosis was subsequently explored using CCK-8, wound healing, Transwell, qRT-PCR and Western blot assays on cell lines. We identified eight pyroptosis markers closely related to endometriosis, among which the expression of NLRP1, PRKACA, and IL-6 were significantly upregulated in patients with endometriosis. The expression patterns of these genes were also confirmed in clinical specimens and cell lines. The results of functional experiments indicated that NLRP1 knockdown inhibited the proliferation, migration, and invasion of 12Z cells. Mechanistic studies revealed that downregulating NLRP1 expression reduced the expression of key molecules in the NF-κB signaling pathway and downstream caspase-1, GSDMD-N. This suggests that NLRP1 promotes pyroptosis by activating the NF-κB signaling pathway, thereby driving the progression of endometriosis. This study reveals a novel mechanism through which NLRP1 activates pyroptosis through the NF-κB signaling pathway and promotes the progression of endometriosis. NLRP1 may serve as a potential diagnostic biomarker and therapeutic target for endometriosis. Similar content being viewed by others

We are grateful to the GEO database for providing data for our research. Funding This study was supported by the National Natural Science Foundation of China (grant number 82403501), Youth Project of Wuxi Municipal Health Commission (grant number Q202218), Medical Key Strategic Project of Wuxi Health Commission and Wuxi Young Scientific and Technological Talents Support Action (grant number TJXD-2024-101). Author information Authors and Affiliations Corresponding authors Ethics declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate This study was approved by the Ethics Committee of Wuxi Maternity and Child Health Care Hospital. Informed consent was obtained from patients for all clinical specimens before collection. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Cong, S., Zhang, B., Dai, S. et al. NLRP1 promotes pyroptosis in endometriosis through the NF-κB signaling pathway. Sci Rep (2026). https://doi.org/10.1038/s41598-026-52642-0 Received: Accepted: Published: DOI: https://doi.org/10.1038/s41598-026-52642-0