Hypoxia-Inducible Factor-1α Promotes Endometrial Stromal Cells Migration and Invasion by Upregulating Autophagy in Endometriosis

Abstract

Endometriosis is a benign gynaecological disease which 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.