scholarly journals GV1001 interacts with androgen receptor to inhibit prostate cell proliferation in benign prostatic hyperplasia by regulating expression of molecules related to epithelial-mesenchymal transition

Aging ◽  
2021 ◽  
Author(s):  
Yejin Kim ◽  
Dahae Lee ◽  
Hyejung Jo ◽  
Cheolhyeon Go ◽  
Jongwon Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Epithelial Mesenchymal Transition ◽  
Prostatic Hyperplasia ◽  
Prostate Cell ◽  
Mesenchymal Transition

scholarly journals NELL2 Modulates Cell Proliferation and Apoptosis via ERK Pathway in the Development of Benign Prostatic Hyperplasia

2021 ◽  
Author(s):  
Jianmin Liu ◽  
Daoquan Liu ◽  
Xueneng Zhang ◽  
Yan Li ◽  
Xun Fu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Benign Prostatic Hyperplasia ◽  
Cell Apoptosis ◽  
Prostatic Hyperplasia ◽  
Human Prostate ◽  
Immunofluorescent Staining ◽  
Erk Pathway ◽  
Prostate Cell ◽  
Mesenchymal Transition ◽  
Dependent Cell

Benign prostatic hyperplasia (BPH) is a quite common illness but its etiology and mechanism remain unclear. Neural epidermal growth factor-like like 2 (NELL2) plays multifunctional roles in neural cell growth and is strongly linked to the urinary tract disease. Current study aims to determine the expression, functional activities and underlying mechanism of NELL2 in BPH. Human prostate cell lines and tissues from normal human and BPH patients were utilized. Immunohistochemical staining, immunofluorescent staining, RT-PCR and Western-blotting were performed. We further generated cell models with NELL2 silenced or overexpressed. Subsequently, proliferation, cycle, and apoptosis of prostate cells were determined by CCK-8 assay and flow cytometry analysis. The epithelial-mesenchymal transition (EMT) and fibrosis process were also analyzed. Our study revealed that NELL2 was upregulated in BPH samples and localized in the stroma and the epithelium compartments of human prostate tissues. NELL2 deficiency induced a mitochondrial-dependent cell apoptosis, and inhibited cell proliferation via phosphorylating ERK1/2 activation. Additionally, suppression of ERK1/2 with U0126 incubation could significantly reverse NELL2 deficiency triggered cell apoptosis. Consistently, overexpression of NELL2 promoted cell proliferation and inhibited cell apoptosis. However, NELL2 interference was observed no effect on EMT and fibrosis process. Our novel data demonstrated that upregulation of NELL2 in the enlarged prostate could contribute to the development of BPH through enhancing cell proliferation and inhibited a mitochondrial-dependent cell apoptosis via the ERK pathway. The NELL2-ERK system might represent an important target to facilitate the development of future therapeutic approaches in BPH.

scholarly journals Targeting Androgen Receptor to Suppress Macrophage-induced EMT and Benign Prostatic Hyperplasia (BPH) Development

2012 ◽  
Vol 26 (10) ◽  
pp. 1707-1715 ◽  
Author(s):  
Tianjing Lu ◽  
Wen-Jye Lin ◽  
Kouji Izumi ◽  
Xiaohai Wang ◽  
Defeng Xu ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Prostatic Hyperplasia ◽  
Sphere Diameter ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Prostate Epithelial Cells ◽  
Emt Markers

Abstract Early studies suggested macrophages might play roles in inflammation-associated benign prostatic hyperplasia (BPH) development, yet the underlying mechanisms remain unclear. Here we first showed that CD68+ macrophages were identified in both epithelium and the stromal area of human BPH tissues. We then established an in vitro co-culture model with prostate epithelial and macrophage cell lines to study the potential impacts of infiltrating macrophages in the BPH development and found that co-culturing prostate epithelial cells with macrophages promoted migration of macrophages. In a three-dimensional culture system, the sphere diameter of BPH-1 prostate cells was significantly increased during coculture with THP-1 macrophage cells. Mechanism dissection suggested that expression levels of epithelial-mesenchymal transition (EMT) markers, such as N-cadherin, Snail, and TGF-β2, were increased, and administration of anti-TGF-β2 neutralizing antibody during co-culture suppressed the EMT and THP-1-mediated growth of BPH-1 cells, suggesting THP-1 might go through EMT to influence the BPH development and progression. Importantly, we found that modulation of androgen receptor (AR) in BPH-1 and mPrE cells significantly increased THP-1 and RAW264.7 cell migration, respectively, and enhanced expression levels of EMT markers, suggesting that AR in prostate epithelial cells might play a role in promoting macrophage-mediated EMT in prostate epithelial cells. Silencing AR function via an AR degradation enhancer, ASC-J9, decreased the macrophage migration to BPH-1 cells and suppressed EMT marker expression. Together, these results provide the first evidence to demonstrate that prostate epithelial AR function is important for macrophage-mediated EMT and proliferation of prostate epithelial cells, which represents a previously unrecognized role of AR in the cross-talk between macrophages and prostate epithelial cells. These results may provide new insights for a new therapeutic approach to battle BPH via targeting AR and AR-mediated inflammatory signaling pathways.

scholarly journals A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

2009 ◽  
Vol 106 (8) ◽  
pp. 2859-2863 ◽  
Author(s):  
Paloma Alonso-Magdalena ◽  
Clemens Brössner ◽  
Angelika Reiner ◽  
Guojun Cheng ◽  
Nobuhiro Sugiyama ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Epithelial Mesenchymal Transition ◽  
Prostatic Hyperplasia ◽  
Mesenchymal Transition

scholarly journals Therapeutic Effects of 25-Hydroxyvitamin D on the Pathological Process of Benign Prostatic Hyperplasia: An In Vitro Evidence

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yanbo Chen ◽  
Hui Xu ◽  
Chong Liu ◽  
Meng Gu ◽  
Qi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Benign Prostatic Hyperplasia ◽  
Prostatic Hyperplasia ◽  
Therapeutic Effects ◽  
Prostate Cell ◽  
Mesenchymal Transition ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

The pathogenesis of benign prostatic hyperplasia (BPH) is extremely complicated which involving the multiple signaling pathways. The deficiency of vitamin D is an important risk factor for BPH, and exogenous vitamin D is effective for the treatment of BPH. In this study, we provided in vitro mechanical evidence of vitamin D as a treatment for BPH using BPH-1, WPMY-1, and PBMC cells. We found that 25-hydroxyvitamin D (25-OH D) level is decreased in BPH and closely correlated with age, prostate volume, maximum flow, international prostate symptom score, and prostate-specific antigen of the BPH patients. We further revealed that 25-OH D ameliorated TGF-β1 induces epithelial-mesenchymal transition (EMT) of BPH-1 cells and proliferation of WPMY-1 cells via blocking TGF-β signaling. Moreover, 25-OH D was able to block NF-κB signaling in PBMCs of BPH patients and STAT3 signaling in BPH cells to relieve inflammation. 25-OH D also protects BPH cells from inflammatory cytokines selected by PBMCs. Finally, we uncovered that 25-OH D alleviated prostate cell oxidative stress by triggering Nrf2 signaling. In conclusion, our data verified that 25-OH D regulated multiple singling pathways to restrain prostate cell EMT, proliferation, inflammation, and oxidative stress. Our study provides in vitro mechanical evidence to support clinical use of vitamin D as a treatment for BPH.

Sign in / Sign up

Export Citation Format

Share Document