MP45-15 TRANSFORMING GROWTH FACTOR BETA 1 INCREASES BENIGN PROSTATIC LUMINAL EPITHELIAL CELL LAYER PERMEABILITY

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2018MP45-15 TRANSFORMING GROWTH FACTOR BETA 1 INCREASES BENIGN PROSTATIC LUMINAL EPITHELIAL CELL LAYER PERMEABILITY Feng Li, Ke Wang, Laura E. Pascal, Yibin Zhou, Morgan Dressel, Donna Stolz, Rajiv Dhir, Joel B. Nelson, Peng Guo, Dalin He, and Zhou Wang Feng LiFeng Li More articles by this author , Ke WangKe Wang More articles by this author , Laura E. PascalLaura E. Pascal More articles by this author , Yibin ZhouYibin Zhou More articles by this author , Morgan DresselMorgan Dressel More articles by this author , Donna StolzDonna Stolz More articles by this author , Rajiv DhirRajiv Dhir More articles by this author , Joel B. NelsonJoel B. Nelson More articles by this author , Peng GuoPeng Guo More articles by this author , Dalin HeDalin He More articles by this author , and Zhou WangZhou Wang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1454AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epithelial barrier permeability appears to be increased in benign prostate hyperplasia (BPH), which correlates with E-Cadherin down-regulation. However, the cause of E-Cadherin down-regulation in BPH is unclear. Transforming growth factor beta 1 (TGF-β1) was found to be up-regulated in clinical BPH specimens and TGF-β1 overexpression induced BPH phenotype in mouse. TGF-β1 was reported to repress the expression of E-Cadherin in benign prostatic cells. However, whether and how TGF-β1 up-regulation affects epithelial barrier permeability is unknown. This research is aimed at examining the change of tight junctions in BPH specimens and exploring the potential role of TGF-β1 in prostatic luminal epithelial permeability. METHODS Prostatic tissues derived from BPH patients or from either donors or patients with low volume prostate cancer were used to study tight junctions in BPH nodules and normal prostate tissues using transmission electron microscopy (TEM). These specimens were also used to study the expression of junctional proteins ZO-1, ZO-2, ZO-3 and E-Cadherin using immunofluorescence staining. Benign prostatic luminal epithelial cell lines BHPrE1 and BPH-1 were utilized to perform in vitro studies. Permeability and tight junctions of cell monolayers in trans-well inserts with/without TGF-β1 treatment were evaluated by trans-epithelium electrical resistant (TER) assay and FITC-dextran trans-well assay, and TEM respectively. Expression of junctional proteins following TGF-β1 treatment was determined by reverse transcription-polymerase chain reaction and western blot. RESULTS Tight junctions as well as junctional proteins were decreased in BPH tissues as compared to the normal prostate, suggesting the compromise of luminal epithelial barriers in BPH. TGF-β1 treatment decreased TER, increased FITC-dextran diffusion, and reduced the formation of tight junctions of cultured BHPrE1 and BPH-1 monolayers, indicating that TGF-β1 disrupted epithelial barrier and increased cell monolayer permeability. TGF-β1 treatment down-regulated the expression of E-Cadherin and Claudin 1 but up-regulated the expression of N-Cadherin, Snail and Slug in BHPrE1 and BPH-1. CONCLUSIONS Tight junctions together with junctional proteins are reduced in BPH specimens and the up-regulation of TGF-β1 is potentially an important mechanism leading to tight junction disruption in BPH pathogenesis. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e603 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Feng Li More articles by this author Ke Wang More articles by this author Laura E. Pascal More articles by this author Yibin Zhou More articles by this author Morgan Dressel More articles by this author Donna Stolz More articles by this author Rajiv Dhir More articles by this author Joel B. Nelson More articles by this author Peng Guo More articles by this author Dalin He More articles by this author Zhou Wang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...