FOXP1 enhances fibrosis via activating Wnt/β-catenin signaling pathway in endometriosis.

Endometriosis is a common gynecological disorder affecting 6-10% women. Endometriosis is associated with excess fibrosis, leading to chronic pain, scarring and aberrant tissue function. However, molecular and cellular mechanisms underlying fibrosis during endometriosis still remain elusive. In this study we used endometrial and endometriotic stromal cells isolated from patients, and employed siRNA to knockdown Forkhead box protein P1 (FOXP1) to investigate the effect of FOXP1 on collagen contraction, cell proliferation and mitigation. Western blot and quantitative PCR were applied for analysis of protein and mRNA levels, respectively. Compared to control stromal cells, endometriotic stromal cells from patients exhibited higher levels of FOXP1 expression and Wnt-related β-catenin acetylation. FOXP1 knockdown decreased not only Wnt signaling, but also the expression of fibrotic marker genes, including connective tissue growth factor, type I collagen, α-smooth muscle actin and fibronectin. Furthermore, FOXP1 knockdown reversed the endometriotic cellular phenotypes, including reducing collagen gel contraction, inhibiting cell proliferation and migration. Finally, Wnt signaling inhibitor AVX939 blocked β-catenin acetylation and endometrial stromal cell proliferation induced by ectopic FOXP1 expression. FOXP1 enhances fibrosis during endometriosis through upregulating Wnt signaling activity.