S100A8/A9 promotes endometrial fibrosis via regulating RAGE/JAK2/STAT3 signaling pathway

Xing Xin; Hao Liu; Siwen Zhang; Pingping Li; Xinyang Zhao; Xudong Zhang; Shuyu Li; Shanshan Wu; Fujie Zhao; Jichun Tan

doi:10.1038/s42003-024-05814-5

Communications Biology (Jan 2024)

S100A8/A9 promotes endometrial fibrosis via regulating RAGE/JAK2/STAT3 signaling pathway

Xing Xin,
Hao Liu,
Siwen Zhang,
Pingping Li,
Xinyang Zhao,
Xudong Zhang,
Shuyu Li,
Shanshan Wu,
Fujie Zhao,
Jichun Tan

Affiliations

Xing Xin: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District
Hao Liu: State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences
Siwen Zhang: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District
Pingping Li: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District
Xinyang Zhao: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District
Xudong Zhang: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District
Shuyu Li: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District
Shanshan Wu: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District
Fujie Zhao: Obstetrics and Gynecology Department, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District
Jichun Tan: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District

DOI: https://doi.org/10.1038/s42003-024-05814-5
Journal volume & issue: Vol. 7, no. 1
pp. 1 – 15

Abstract

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Abstract Intrauterine adhesion (IUA) is characterized by endometrial fibrosis. S100A8/A9 plays an important role in inflammation and fibroblast activation. However, the role of S100A8/A9 in IUA remains unclear. In this study, we collect normal and IUA endometrium to verify the expression of S100A8/A9. Human endometrial stromal cells (hEnSCs) are isolated to evaluate fibrosis progression after S100A8/A9 treatment. A porcine IUA model is established by electrocautery injury to confirm the therapeutic effect of menstrual blood-derived stromal cells (MenSCs) on IUA. Our study reveals increased S100A8/A9 expression in IUA endometrium. S100A8/A9 significantly enhances hEnSCs proliferation and upregulates fibrosis-related and inflammation-associated markers. Furthermore, S100A8/A9 induces hEnSCs fibrosis through the RAGE-JAK2-STAT3 pathway. Transplantation of MenSCs in a porcine IUA model notably enhances angiogenesis, mitigates endometrial fibrosis and downregulates S100A8/A9 expression. In summary, S100A8/A9 induces hEnSCs fibrosis via the RAGE-JAK2-STAT3 pathway, and MenSCs exhibit marked effects on endometrial restoration in the porcine IUA model.

Published in Communications Biology

ISSN: 2399-3642 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General)
Website: https://www.nature.com/commsbio/

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