COX2 is induced in the ovarian epithelium during ovulatory wound repair and promotes cell survival†.

ABSTRACT: The ovarian surface epithelium (OSE) is a monolayer of cells surrounding the ovary that is ruptured during ovulation. After ovulation, the wound is repaired, however, this process is poorly understood. In epithelial tissues, wound repair is mediated by an epithelial-to-mesenchymal transition (EMT). Transforming Growth Factor Beta-1 (TGF?1) is a cytokine commonly known to induce an EMT and is present throughout the ovarian microenvironment. We, therefore, hypothesized that TGF?1 induces an EMT in OSE cells and activates signaling pathways important for wound repair. Treating primary cultures of mouse OSE cells with TGF?1 induced an EMT mediated by TGF?RI signaling. The transcription factor Snail was the only EMT-associated transcription factor increased by TGF?1 and, when overexpressed, was shown to increase OSE cell migration. A polymerase chain reaction array of TGF? signaling targets determined Cyclooxygenase-2 (Cox2) to be most highly induced by TGF?1. Constitutive Cox2 expression modestly increased migration and robustly enhanced cell survival, under stress conditions similar to those observed during wound repair. The increase in Snail and Cox2 expression with TGF?1 was reproduced in human OSE cultures, suggesting these responses are conserved between mouse and human. Finally, the induction of Cox2 expression in OSE cells during ovulatory wound repair was shown in vivo, suggesting TGF?1 increases Cox2 to promote wound repair by enhancing cell survival. These data support that TGF?1 promotes ovulatory wound repair by induction of an EMT and activation of a COX2-mediated pro-survival pathway. Understanding ovulatory wound repair may give insight into why ovulation is the primary non-hereditary risk factor for ovarian cancer.

SUBMITTER: Carter LE 

PROVIDER: S-EPMC6877777 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature