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Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function.
Chen, Pei; Ye, Chaoshuang; Huang, Yunke; Xu, Bingning; Wu, Tianyu; Dong, Yuanhang; Jin, Yang; Zhao, Li; Hu, Changchang; Mao, Jingxia; Wu, Ruijin.
Afiliação
  • Chen P; Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Ye C; Key Laboratory of Women's Reproductive Health of Zhejiang Province, Hangzhou, China.
  • Huang Y; Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Xu B; Key Laboratory of Women's Reproductive Health of Zhejiang Province, Hangzhou, China.
  • Wu T; Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Dong Y; Key Laboratory of Women's Reproductive Health of Zhejiang Province, Hangzhou, China.
  • Jin Y; Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Zhao L; Key Laboratory of Women's Reproductive Health of Zhejiang Province, Hangzhou, China.
  • Hu C; Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Mao J; Key Laboratory of Women's Reproductive Health of Zhejiang Province, Hangzhou, China.
  • Wu R; Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Biol Res ; 57(1): 13, 2024 Apr 01.
Article em En | MEDLINE | ID: mdl-38561846
ABSTRACT

BACKGROUND:

Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis.

METHODS:

The activation model of ESCs was constructed by TGF-ß1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis.

RESULTS:

We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes.

CONCLUSION:

Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glutamina / Mitocôndrias Limite: Animals / Female / Humans Idioma: En Revista: Biol Res Assunto da revista: BIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glutamina / Mitocôndrias Limite: Animals / Female / Humans Idioma: En Revista: Biol Res Assunto da revista: BIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido