Work

Ectopic endometrial stromal cells‐derived exosomes accelerate endometriosis progression by delivering PDLIM3 to induce macrophage M2 polarization

Year: 2026

Type: article

Abstract: Endometriosis (Ems) is a benign disease characterized by invasion and migration. Abnormally expressed mRNAs regulate its progression. In this study, we analyzed GEO datasets and identified significant upregulation of PDLIM3 in ectopic endometrial tissues. Our aim was to explore the role of PDLIM3 and its regulatory mechanisms in Ems progression. Using bioinformatics, we analyzed differentially expressed genes and treated endometrial stromal cells (ESCs) with modified PDLIM3 and PRMT1 expression vectors to assess their impact on Ems. We measured macrophage polarization markers and the secreted cytokines as well as the percentage of CD206‐positive macrophages to evaluate the PDLIM3/NAA40/PRMT1 axis's influence on macrophage polarization. Also, we tested the impact of THP‐1‐derived macrophages (THP‐1‐DM) under different conditions on ESCs. An animal model was developed to study the effects of PDLIM3 carried by exosomes from ectopic ESCs (ecESCs‐Exos) on macrophage M2 polarization and Ems progression. M2 macrophages enhance ecESCs proliferation and migration, with PDLIM3 delivered by exosomes from ecESCs inducing M2 macrophage polarization. Mechanistically, PDLIM3 binds to NAA40 to suppress its ubiquitination and thus stabilize its protein. Then, the enhanced NAA40 binds to PRMT1 promoter and promotes asymmetric dimethylation of H4 histone to activate PRMT1, hence driving M2 macrophage polarization. In turn, in vitro data showed that ecESCs‐Exos‐induced M2 macrophages via PDLIM3/PRMT1 axis further accelerates ESCs proliferation and migration. Moreover, in vivo data demonstrate that exosomal PDLIM3 accelerates Ems progression via contributing to macrophage M2 polarization. Exosomal PDLIM3 from ecESCs contributes to Ems progression by inducing M2 macrophage polarization. The findings provide new clues regarding the progression of Ems, which might be beneficial for developing new therapeutic targets for Ems patients.

Source: Journal of Cell Communication and Signaling

DOI: 10.1002/ccs3.70122