Hypoxia-inducible factor-1α promotes endometrial stromal cells migration and invasion by upregulating autophagy in endometriosis.
Reproduction
; 153(6): 809-820, 2017 06.
Article
en En
| MEDLINE
| ID: mdl-28348069
ABSTRACT
Endometriosis is a benign gynecological disease that shares some characteristics with malignancy like migration and invasion. It has been reported that both hypoxia-inducible factor-1α (HIF-1α) and autophagy were upregulated in ectopic endometrium of patients with ovarian endometriosis. However, the crosstalk between HIF-1α and autophagy in the pathogenesis of endometriosis remains to be clarified. Accordingly, we investigated whether autophagy was regulated by HIF-1α, as well as whether the effect of HIF-1α on cell migration and invasion is mediated through autophagy upregulation. Here, we found that ectopic endometrium from patients with endometriosis highly expressed HIF-1α and autophagy-related protein LC3. In cultured human endometrial stromal cells (HESCs), autophagy was induced by hypoxia in a time-dependent manner and autophagy activation was dependent on HIF-1α. In addition, migration and invasion ability of HESCs were enhanced by hypoxia treatment, whereas knockdown of HIF-1α attenuated this effect. Furthermore, inhibiting autophagy with specific inhibitors and Beclin1 siRNA attenuated hypoxia triggered migration and invasion of HESCs. Taken together, these results suggest that HIF-1α promotes HESCs invasion and metastasis by upregulating autophagy. Thus, autophagy may be involved in the pathogenesis of endometriosis and inhibition of autophagy might be a novel therapeutic approach to the treatment of endometriosis.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Autofagia
/
Movimiento Celular
/
Células del Estroma
/
Endometriosis
/
Endometrio
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Proteínas Asociadas a Microtúbulos
Límite:
Adult
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Reproduction
Asunto de la revista:
MEDICINA REPRODUTIVA
Año:
2017
Tipo del documento:
Article
País de afiliación:
China