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

Lan Y, Yi Lan, Wang L, Lan Wang, Huang Z, Zhen Huang, Ren S, Siling Ren, Tang L, Liangdan Tang
Scientific reports · 2026 · vol. 16(1) · doi:10.1038/s41598-026-44527-z · PMID:42034852 · PMC13279817 · W7155602038
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⚙ AI-generated summary by claude@2026-07, 2026-07-17 ⓘ

SIRT1 deacetylation of HMGB1 stabilizes the protein, promoting autophagy and enhancing the invasiveness of endometrial cells, thereby driving endometriosis progression.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 · read from full text ⓘ

The paper investigated whether SIRT1-mediated deacetylation regulates HMGB1 and influences progression of endometriosis, using normal, ectopic, and eutopic endometrial tissues from patients as well as human endometrial stromal cells (HESCs) and an endometriosis rat model. RT-qPCR and Western blot showed elevated SIRT1 expression in both eutopic and ectopic tissues, while SIRT1 deficiency suppressed HESC viability, migration, invasion, an observed phenotypic shift, and autophagy; mechanistically, SIRT1 deficiency reduced HMGB1 protein stability. HMGB1 overexpression increased HESC viability, migration, invasion, autophagy, and promoted the phenotypic switch (decreased mesenchymal markers such as vimentin and N-cadherin with increased E-cadherin), and in rats SIRT1 silencing suppressed this phenotypic switch and autophagy in uterine tissue. This paper is centrally about endometriosis — it tests how SIRT1 deacetylation of HMGB1 promotes endometriosis progression through regulation of autophagy.

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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.
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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

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Condition tags

endometriosis

MeSH descriptors

Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy

Citation neighborhood

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. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (43)

SciLite annotations

chemicals 48
estrogen acetyl acetyl lysine progestin nitrogen lysine arginine 3-methyladenine c15-(r)-methylthienyl rapamycin chloroquine chartaceone a bafilomycin a1 vinylidene fluoride leucomethylene blue dimethyl ethynylboronate calcium methanol crystal violet agarose agarose lysine lysine cycloheximide water amyloid-beta benzoate tribromoethanol ampicillin sodium estradiol benzoate water estradiol sodium pentobarbital formaldehyde haematoxylin diethylcarbamazine citrate hydrogen peroxide haematoxylin c15-(r)-methylthienyl rapamycin chloroquine bafilomycin a1 estrogen d-glucopyranosyl-(1->3)-d-mannopyranose histone lysine
organisms 38
eukaryotes human pleuropneumonia pleuropneumonia pleuropneumonia rabbits human zitter rats transgenic mice human naine d'afrique de l'ouest rabbits human rodents tachyoryctes rattus sp. rattus sp. rattus sp. rattus sp. rattus sp. rattus sp. lentivirus lentivirus rattus sp. rattus sp. rodents rabbits rattus sp. rodents rattus sp. human human human rattus sp. rodents human zitter rats zitter rats

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