SIRT1-mediated deacetylation of HMGB1 promotes the progression of endometriosis by regulating autophagy

Abstract Endometriosis (EMs) is a disease characterized by the presence of endometrial tissue outside the uterus, which often causes pain, abnormal bleeding, and infertility. Sirtuin 1 (SIRT1)-mediated deacetylation is implicated in the progression of various diseases, yet its role in EMs remains unexplored. Normal, ectopic, and eutopic endometrial tissues from EMs or non-EMs patients were collected. RT-qPCR and Western blot analyses were performed to evaluate SIRT1 expression. Cell viability, migration, and invasion of human endometrial stromal cells (HESCs) were assessed using the MTT assay, Transwell migration, and invasion assays. Protein levels were analyzed via Western blot. The interaction between SIRT1 and high mobility group box 1 (HMGB1) was examined using co-immunoprecipitation. Finally, an EMs rat model was developed. Results demonstrated that both eutopic and ectopic endometrial tissues exhibited elevated SIRT1 expression. Furthermore, SIRT1 deficiency suppressed HESC viability, migration, invasion, and a phenotypic shift, as well as autophagy. Mechanistically, SIRT1 deficiency reduced HMGB1 protein stability in HESCs. Additionally, HMGB1 overexpression enhanced HESC viability, migration, invasion, autophagy, and induced a phenotypic switch characterized by downregulation of mesenchymal markers (e.g., vimentin, N-cadherin) and upregulation of the epithelial marker E-cadherin. In the rat model, SIRT1 silencing suppressed this phenotypic switch and autophagy in uterine tissue. Collectively, SIRT1-mediated deacetylation of HMGB1 at lysine 12 stabilized HMGB1 protein, promoting autophagy and enhancing the invasive and migratory capacity of HESCs, thus driving EMs progression—offering novel therapeutic insights for EMs treatment. Similar content being viewed by others Author information Authors and Affiliations Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate The clinical study was approved by the Ethics Committee of The First Affiliated Hospital of Chongqing Medical University. Informed consent was obtained from all individual participants included in the study. This study was performed in line with the principles of the Declaration of Helsinki. The animal study was approved by the Ethics Committee of MDKN Biotechnology Co., Lt. All animal experiments complied with the ARRIVE guidelines. All methods were carried out in accordance with relevant guidelines and regulations. 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 Lan, Y., Wang, L., Huang, Z. et al. SIRT1-mediated deacetylation of HMGB1 promotes the progression of endometriosis by regulating autophagy. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44527-z Received: Accepted: Published: DOI: https://doi.org/10.1038/s41598-026-44527-z