FGF7 Induces Epithelial-mesenchymal Transition In Epithelial Cells During The Progression Of Benign Prostatic Hyperplasia(BPH)with Intravesical Prostatic Protrusion And Small Volume Via The MAPK-ERK1/2 Signaling Pathway

Background: Benign prostatic hyperplasia(BPH)is a progressive disease in elderly men.Patients with prostatic hyperplasia in the middle lobe that protrudes into the bladder suffer more serious lower urinary tract symptoms.This phenomenon attracted our attention.To search for potential factors that may be associated with this interesting clinical phenomenon,we collected prostate tissues from patients and performed gene array analyses.The results showed that fibroblast growth factor 7was highly expressed in the hyperplastic middle lobe of prostate compared to normal prostate tissue.Therefore,we investigate the potential effect of FGF7 on the progression of hyperplasia of the middle prostate lobe and the mechanisms of FGF7 in promoting the development of this clinical phenotype.Methods: Stromal cells were obtained from the middle lobe of hyperplastic and normal prostates.An FGF7 siRNA vector was constructed and transfected into hyperplastic stromal and BPH-1 cells.RWPE-1 cells were treated with 50,100,and200 ng/ml of FGF7 for 48 h.Cell proliferation was evaluated using a CCK-8 assay.ELISA was used to measure the levels of FGF7.Multiple proteins were assessed via Western blotting.Results: Western blot results showed that FGF7 levels in BPH-1 cells were higher than in RWPE-1 cells.The results of ELISA analysis suggested that the level of FGF7 protein in the culture supernatant was increased in hyperplastic stromal cells compared with normal stromal cells.In vitro cell culture showed that knock down of FGF7 in BPH-1 cells suppressed proliferation,and the stimulation of FGF7 in RWPE-1 cells promoted proliferation.We found that the expression levels of epithelial-mesenchymal transition(EMT)markers,such as N-cadherin and Snail,increased in RWPE-1 cells stimulated with FGF7.Following the downregulation of FGF7 in BPH-1 cells,these markers exhibited a decreasing trend.ERK1/2phosphorylation decreased following FGF7 knockdown in BPH-1 cells.Conclusion:FGF7 not only promoted the proliferation of epithelial cells but also induced epithelial-mesenchymal transition during the development of BPH with intravesical middle-lobe prostatic protrusion.Our results suggest that FGF7 may be responsible for the hyperplasia of the middle prostate lobe,and these results provide a potential treatment plan for this clinical phenotype of BPH.