Abstract / Summary
Benign prostatic hyperplasia (BPH) is a progressive disease in elderly men, the mechanism of which remains unclear. The aim of this study was to explore how autophagy inhibition in BPH epithelial cells influences BPH progression. Paraffin-embedded prostate specimens were classified into two groups based on hematoxylin-eosin (HE) staining: stromal hyperplasia (SH, n = 25) and glandular epithelial hyperplasia (EH, n = 17). The autophagy level in epithelial cells of the SH group was markedly reduced compared with the EH group, as evaluated via immunohistochemistry. Chloroquine (CQ) was employed to suppress autophagy in BPH-1 cells. Conditioned media (CM) were harvested and utilized for treating the WPMY-1 cell line and primary prostatic stromal cells (PPrSCs). CCK-8 assays were employed to assess cell proliferation. qRT-PCR and ELISA were utilized to quantify cytokines and growth factors. Treatment of WPMY-1 and PPrSC cells with CM from autophagy-inhibited BPH-1 cells significantly enhanced their proliferation. FGF6 levels were significantly elevated in CM from BPH-1 cells treated with CQ. Recombinant FGF6 protein stimulated proliferation in WPMY-1 and PPrSC cells, and the AKT and ERK signaling pathways were activated following treatment with BPH-1 CM or recombinant FGF6, an effect that could be reversed by FGF6 neutralizing antibody. The expression level of FGF6 in the SH group was significantly higher than that in the EH group. Meanwhile, in the SH group, the expression of FGF6 was negatively correlated with the expression of LC3. Autophagy suppression in prostate epithelial cells results in the secretion of substantial amounts of FGF6, which promotes fibroblast proliferation and accelerates BPH progression.