Effects of small-molecule antagonists of the Tcf/β-catenin complex (PKF 115-584 and CGP049090) on stromal cell-mediated collagen gel contraction.

Sachiko Matsuzaki (405488), Claude Darcha (405489)
2015 · doi:10.1371/journal.pone.0076808.g003 · W6960233374
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The study investigated the role of Wnt/β-catenin signaling in endometriosis by treating stromal cells from patients with and without the disease, as well as those with ovarian or deep infiltrating lesions, with small-molecule antagonists PKF 115-584 and CGP049090. Results demonstrated that these inhibitors significantly reduced collagen gel contraction mediated by both endometrial and endometriotic stromal cells, with notable differences observed between cell types derived from different disease phenotypes. The findings indicate that blocking the Tcf/β-catenin complex can suppress fibrotic processes associated with endometriosis in vitro. This paper is centrally about endometriosis — specifically examining the molecular mechanisms of fibrosis in endometriotic stromal cells and their response to Wnt pathway inhibition.

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Abstract

A–F: Collagen gel contraction at 0, 4, 8, 12, and 24 h in matched endometrial and endometriotic stromal cells from the same patient (A), *: p<.05: EES:deep endometriosis versus EES: ovarian endometriosis, endometrial stromal cells of patients with and without endometriosis (B), *: p<.05: versus EuEs: patients with endometriosis, treated and vehicle-treated endometrial stromal cells of patients with (C), *: p<.05: versus treated EuEs, and without endometriosis (D), *: p<.05: versus treated EuEs, treated and vehicle-treated endometriotic stromal cells (E, F), *: p<.05: versus treated EES, and G, H: Representative photomicrographs of contracted gels taken at 24 h in endometriotic stromal cells with and without treatment.\nNumerical values are presented as the mean + SEM.\nEES: endometriotic stromal cells; EuES: endometrial stromal cells.\nEndo (-): endometrium of patients without endometriosis.\nEndo (+): Endometrium of patients with endometriosis.\nEuES: ovarian endometriosis (n=10); EES: ovarian endometriosis (n=10).\nEuES: deep endometriosis (n=10); EES: deep endometriosis (n=10).\nEuES: patients with endometriosis (n=20); EuES: patients without endometriosis (n=10).
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Involvement of the Wnt/β-Catenin Signaling Pathway in the Cellular and Molecular Mechanisms of Fibrosis in Endometriosis Figure 3 Effects of small-molecule antagonists of the Tcf/β-catenin complex (PKF 115-584 and CGP049090) on stromal cell-mediated collagen gel contraction. A–F: Collagen gel contraction at 0, 4, 8, 12, and 24 h in matched endometrial and endometriotic stromal cells from the same patient (A), *: p<.05: EES:deep endometriosis versus EES: ovarian endometriosis, endometrial stromal cells of patients with and without endometriosis (B), *: p<.05: versus EuEs: patients with endometriosis, treated and vehicle-treated endometrial stromal cells of patients with (C), *: p<.05: versus treated EuEs, and without endometriosis (D), *: p<.05: versus treated EuEs, treated and vehicle-treated endometriotic stromal cells (E, F), *: p<.05: versus treated EES, and G, H: Representative photomicrographs of contracted gels taken at 24 h in endometriotic stromal cells with and without treatment. Numerical values are presented as the mean + SEM. EES: endometriotic stromal cells; EuES: endometrial stromal cells. Endo (-): endometrium of patients without endometriosis. Endo (+): Endometrium of patients with endometriosis. EuES: ovarian endometriosis (n=10); EES: ovarian endometriosis (n=10). EuES: deep endometriosis (n=10); EES: deep endometriosis (n=10). EuES: patients with endometriosis (n=20); EuES: patients without endometriosis (n=10).

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