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

Commun Biol. 2024 Jan 22;7(1):116. doi: 10.1038/s42003-024-05814-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calgranulin A / genetics
  • Endometrium
  • Epithelial Cells
  • Female
  • Humans
  • Inflammation
  • Janus Kinase 2 / genetics
  • STAT3 Transcription Factor
  • Swine
  • Uterine Diseases*

Substances

  • Calgranulin A
  • JAK2 protein, human
  • Janus Kinase 2
  • STAT3 protein, human
  • STAT3 Transcription Factor