npj agingJul 24, 2026

FOSL2-related cell aging in the uterine lining promotes inflammation in endometriosis

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 25, 2026

Abstract

A subgroup of endometrial stromal cells in endometriosis patients shows overexpression of the FOSL2 transcription factor.

The senescence-associated secretory phenotype (SASP) is identified in endometrial stromal cells from both healthy tissue and lesions in endometriosis patients.
FOSL2 overexpression in these cells promotes cellular aging and the secretion of pro-inflammatory factors associated with SASP.
Knocking down FOSL2 reverses the effects of SASP, suggesting its key role in regulating this inflammatory response.
Conditioned medium from cells with high FOSL2 levels encourages the polarization and recruitment of M2 macrophages, which are linked to inflammation.
The PGE2/cAMP/PKA signaling pathway regulates FOSL2 overexpression, while FOSL2 influences SASP via NF-κB signaling.
The SASP in endometrial stromal cells may contribute to chronic pelvic inflammation and immune disruption in endometriosis.

Simplified

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.

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PubMed

FOSL2-related cell aging in the uterine lining promotes inflammation in endometriosis

Abstract

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