Hypoxia activates the hypoxia-inducible factor-1α/vascular endothelial growth factor pathway in a prostatic stromal cell line:A mechanism for the pathogenesis of benign prostatic hyperplasia  

作　　者：Tao Zhang Changlin Mao Yao Chang Jiaju Lyu Delong Zhao Sentai Ding 

机构地区：[1]Department of Urology,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan,China [2]Department of Urology,Mindong Hospital Affiliated to Fujian Medical University,Fuan,China

出　　处：《Current Urology》2024年第3期185-193,共9页当代泌尿学（英文）

基　　金：the financial support granted from the Shandong Province Key Research and Development Projects(no.2016GSF201147);the Science and Technology Development Program of Jinan(no.201704127).

摘　　要：Background The development of benign prostatic hyperplasia(BPH)is closely related to hypoxia in the prostatic stroma,and the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)pathway has been shown to significantly activate in response to hypoxia.The underlying mechanism for activation of this pathway in the pathogenesis of BPH remains unclear.Materials and methods We constructed HIF-1αoverexpression and knockdown BPH stromal(WPMY-1)and epithelial(BPH-1)cell lines,which were cultured under different oxygen conditions(hypoxia,normoxia,and hypoxia+HIF-1αinhibitor).Quantitative real-time polymerase chain reaction(qPCR)and Western blotting were applied to detect the expression of the HIF-1α/VEGF pathway.Cell proliferation and apoptosis were analyzed by Cell Counting Kit-8 and flow cytometry.We used the miRWalk 2.0 database and Western blotting to predict the potential miRNA that selectively targets the HIF-1α/VEGF pathway,and verified the prediction by qPCR and dual-luciferase assays.Results In a BPH stromal cell line(WPMY-1),the expression of VEGF was in accordance with HIF-1αlevels,elevated in the overexpression cells and decreased in the knockdown cells.Hypoxia-induced HIF-1αoverexpression,which could be reversed by a HIF-1αinhibitor.Moreover,the HIF-1αinhibitor significantly depressed cellular proliferation and promoted apoptosis in hypoxic conditions,assessed by Cell Counting Kit-8 and flow cytometry.However,in the BPH epithelial cell line(BPH-1),the expression level of HIF-1αdid not influence the expression of VEGF.Finally,a potential miRNA,miR-17-5p,regulating the HIF-1α/VEGF pathway was predicted from the miRWalk 2.0 database and Western blotting,and verified by qPCR and dual-luciferase assay.Conclusions In hypoxia,activation of the HIF-1α/VEGF pathway plays a crucial role in regulating cell proliferation in a BPH stromal cell line.Regulation by miR-17-5p may be the potential mechanism for the activation of this pathway.Regulation of this pathway may be involved in the pa

关 键 词：Benign prostatic hyperplasia Hypoxia-inducible factor-1α Vascular endothelial growth factor PATHOGENESIS miR-17-5p 

分 类 号：R697.32[医药卫生—泌尿科学]