Increased expression of YAP is associated with decreased cell autophagy in the eutopic endometrial stromal cells of endometriosis

Abstract

Basic research has shown that signal pathways play significant roles in the development and progression of endometriosis (EMS). We first reported that the Hippo-YAP (Yes-associated protein) pathway promotes cell proliferation and anti-apoptosis in endometrial stromal cells (ESCs) of EMS. Cell autophagy has been found to be involved in the endometrial regulation and the pathophysiology of EMS. We speculated that there may be an elaborate dialogue between Hippo-YAP and autophagy pathway in EMS. To explore this, we performed molecular biology experiments to investigate the expressions of YAP pathway and cell autophagy markers (mTOR, LC-3) in ESCs of women with or without EMS and detected the protein levels of autophagy markers after verteporfin and rapamycin treatments and the transfection with YAP-knockdown vector in the eutopic ESCs, respectively. We found that the mRNAs of YAP and mTOR were increased in the eutopic ESCs compared with controls, but no statistically difference, while the protein levels were significantly increased in the eutopic ESCs. Conversely, the ratio of the autophagy marker protein LC3-II/LC3-I was significantly decreased in the eutopic ESCs compared with controls. Moreover, verteporfin treatment interfered with the YAP function, but it had no effect on mTOR expression and cell autophagy level. Rapamycin treatment and YAP knockdown in the eutopic ESCs both inhibited the expression of YAP and increased the ratio of LC3-II/LC3-I significantly. These results demonstrate that the decreased cell autophagy level is associated with the increased expression of YAP and YAP may participate in the mTOR-autophagy pathway in the eutopic ESCs of endometriosis.

Keywords: Cell autophagy; Endometrial stromal cells; Endometriosis; Yes-associated protein (YAP); mTOR.