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<p>Endometriosis (EMs) is characterized by chronic pelvic inflammation, but the etiology of this inflammation remains poorly understood. The senescence-associated secretory phenotype (SASP), whereby senescent cells secrete pro-inflammatory cytokines, is a potential mechanism. This study investigates the pro-inflammatory SASP in EMs and its underlying influences. Through molecular assays and single-cell RNA-seq analysis, we found a subgroup of endometrial stromal cells (ESCs) marked by SASP in both eutopic endometrium and endometriotic lesions of EMs patients. The transcription factor FOSL2 was aberrantly overexpressed in this ESC subgroup; its overexpression induced cellular senescence and the secretion of SASP factors, while FOSL2 knockdown reversed these effects. Conditioned medium from ESCs with high FOSL2 expression promoted M2 macrophage polarization and recruitment. Mechanistically, FOSL2 overexpression in ESCs was regulated by the PGE2/cAMP/PKA signaling pathway, and FOSL2 modulated SASP through the activation of NF-κB signaling. In conclusion, the SASP in ESCs, regulated by FOSL2, contributes to chronic pelvic inflammation and immune system disruption in EMs patients. Targeting FOSL2 to reverse the SASP may offer a promising therapeutic strategy for EMs.</p><p></p>

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FOSL2-driven SASP in endometrial stroma promotes the inflammation of endometriosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月24日

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  • Weiwei Shi,
  • Xinyi Tang,
  • Fei Yang,
  • Han Yin,
  • Quan Zhou,
  • Fangyue Sun,
  • Shanbo Ding,
  • Udo Jeschke,
  • Lin Peng

摘要

Endometriosis (EMs) is characterized by chronic pelvic inflammation, but the etiology of this inflammation remains poorly understood. The senescence-associated secretory phenotype (SASP), whereby senescent cells secrete pro-inflammatory cytokines, is a potential mechanism. This study investigates the pro-inflammatory SASP in EMs and its underlying influences. Through molecular assays and single-cell RNA-seq analysis, we found a subgroup of endometrial stromal cells (ESCs) marked by SASP in both eutopic endometrium and endometriotic lesions of EMs patients. The transcription factor FOSL2 was aberrantly overexpressed in this ESC subgroup; its overexpression induced cellular senescence and the secretion of SASP factors, while FOSL2 knockdown reversed these effects. Conditioned medium from ESCs with high FOSL2 expression promoted M2 macrophage polarization and recruitment. Mechanistically, FOSL2 overexpression in ESCs was regulated by the PGE2/cAMP/PKA signaling pathway, and FOSL2 modulated SASP through the activation of NF-κB signaling. In conclusion, the SASP in ESCs, regulated by FOSL2, contributes to chronic pelvic inflammation and immune system disruption in EMs patients. Targeting FOSL2 to reverse the SASP may offer a promising therapeutic strategy for EMs.