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Cytokine ; 125: 154850, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557635

RESUMO

BACKGROUND: Endometrial injury can result in thin endometrium and subfertility. Granulocyte macrophage colony stimulating factor (GM-CSF) contributes to tissue repair, but its role in endometrial regeneration has not been investigated. METHODS: To determine the effect of GM-CSF on endometrial regeneration, we established a mouse model of thin endometrium by uterine perfusion with 20 µL 90% ethanol. Thin endometrium in mice was featured by lowered endometrial thickness, decreased expression of Ki67 in glandular cells, and a reduced number of implantation sites. To explore the mechanism of GM-CSF on endometrial regeneration, endometrium was obtained from patients undergoing hysterectomy or hysteroscopy and endometrial biopsy. Effects of GM-CSF on primary cultured human endometrial glandular and stromal cells were examined by the 5-bromo-2'-deoxyuridine (BrdU) proliferation assay and transwell migration assay, followed by exploration of the potential signaling pathway. RESULTS: GM-CSF intraperitoneal (i.p.) injection significantly increased endometrial thickness, expression of Ki67 in endometrial glandular cells, and the number of implantation sites. GM-CSF significantly promoted proliferation of primary human endometrial glandular cells and migration of stromal cells. GM-CSF activated p-Akt and increased expressions of p70S6K and c-Jun, which were blocked by LY294002. CONCLUSION: We found that GM-CSF could improve endometrial regeneration, possibly through activating PI3K/Akt signaling pathway.


Assuntos
Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Regeneração/efeitos dos fármacos , Adulto , Animais , Biópsia , Bromodesoxiuridina/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Histerectomia , Injeções Intraperitoneais , Janus Quinases/metabolismo , Antígeno Ki-67/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Pessoa de Meia-Idade , Morfolinas/farmacologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo
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