Phosphatase and tensin homolog deficiency induces M2 macrophage polarization by promoting glycolytic activity in endometrial stromal cells

作者：Fengqin Dai, Jinjin Li, Yingwei Liu · 发表于：Biology of Reproduction · 年份：2025 · DOI：10.1093/biolre/ioaf016 · 被引用次数：8 · 研究领域：Endometriosis Research and Treatment、Reproductive System and Pregnancy、Endometrial and Cervical Cancer Treatments

Endometriosis is a common gynecological disorder, whose pathogenesis remains incompletely understood. Macrophages, a key type of immune cell, are pivotal in the context of endometriosis. This study seeks to explore the interactions between endometriotic cells and macrophages. Quantitative real-time PCR (qRT-PCR) and Western blot experiments were employed to detect phosphatase and tensin homolog (PTEN) expression. Glucose consumption, lactate production, extracellular acidification rate, and oxygen consumption rate levels were used to assess cellular glycolytic capacity. The interaction between conditioned media from ectopic endometrial stromal cells (EESCs) and macrophages was investigated through co-culture experiments. The expression of M2 macrophage marker proteins and inflammatory factors was detected via qRT-PCR, immunofluorescence staining, and enzyme-linked immunosorbent assay. Cellular functions were evaluated using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU), and wound healing assays. We found that PTEN deficiency promoted the glycolytic activity of EESCs. Simultaneously, it significantly promoted the macrophages' polarization toward the M2 phenotype, demonstrated by increased expression of M2 markers (differentiation 206 (CD206), CD163, and (C-C motif) ligand 22 (CCL22)). Further studies revealed that PTEN-deficient EESCs increased the level of CCL2 via promoting glycolytic activity, which was reversed by glycolytic inhibitor. Moreover, lactate and conditio...