Scholarlink

<p>Abnormal accumulation of prostaglandin E2 (PGE2) is a secondary effect of the presence of bacterial infection, and usually causes overproduction of proinflammatory cytokines, thereby leading to infiltration of neutrophils, serving as a key etiology of endometritis linking to infertility. Metastasis-associated protein 1 (MTA1), functioning as a master transcriptional coregulator, is increasingly recognized as an important influencer of inflammation, but its functional roles in endometritis, if any, remain unexplored. Herein, by investigating clinical correlations, in vitro assays, and uterus-specific <i>Mta1</i> knockouts, we show that MTA1 expression was significantly downregulated in endometrial biopsies from patients with chronic endometritis (CE) and in human endometrial stromal cells (HESCs) challenged with clinically relevant pathogenic dosage of lipopolysaccharide (LPS). MTA1 deletion augmented endometrial neutrophil infiltration, exacerbated inflammatory phenotype and negatively affected the outcome of LPS-induced endometritis through modulation of PGE2 secretion. We have also identified cyclooxygenase-2 (COX2) as the key rate-limiting enzyme responsible for the deregulated PGE2 synthesis in MTA1 deficiency-exacerbated endometritis. Mechanistically, MTA1 negatively regulated the transcription of <i>Cox2</i>, likely in collaboration with HDAC2 (histone deacetylase 2), in LPS-challenged endometrial stromal cells (ESCs). In summary, MTA1 signaling may govern appropriate inflammatory response in ESCs against the pathogenesis of endometritis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

MTA1-mediated transcriptional repression of Cox2 confers resistance against neutrophil infiltration in endometritis

  • 期刊论文

  • 发表日期：

    2026年3月10日

查看全文
  • Mao Li,
  • Junting Li,
  • Huan Li,
  • Fang Liu,
  • Yang Yang,
  • Ruifang An

摘要

Abnormal accumulation of prostaglandin E2 (PGE2) is a secondary effect of the presence of bacterial infection, and usually causes overproduction of proinflammatory cytokines, thereby leading to infiltration of neutrophils, serving as a key etiology of endometritis linking to infertility. Metastasis-associated protein 1 (MTA1), functioning as a master transcriptional coregulator, is increasingly recognized as an important influencer of inflammation, but its functional roles in endometritis, if any, remain unexplored. Herein, by investigating clinical correlations, in vitro assays, and uterus-specific Mta1 knockouts, we show that MTA1 expression was significantly downregulated in endometrial biopsies from patients with chronic endometritis (CE) and in human endometrial stromal cells (HESCs) challenged with clinically relevant pathogenic dosage of lipopolysaccharide (LPS). MTA1 deletion augmented endometrial neutrophil infiltration, exacerbated inflammatory phenotype and negatively affected the outcome of LPS-induced endometritis through modulation of PGE2 secretion. We have also identified cyclooxygenase-2 (COX2) as the key rate-limiting enzyme responsible for the deregulated PGE2 synthesis in MTA1 deficiency-exacerbated endometritis. Mechanistically, MTA1 negatively regulated the transcription of Cox2, likely in collaboration with HDAC2 (histone deacetylase 2), in LPS-challenged endometrial stromal cells (ESCs). In summary, MTA1 signaling may govern appropriate inflammatory response in ESCs against the pathogenesis of endometritis.