Dataset Information

A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).

ABSTRACT: Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common conditions. Little is known about their etiologies except that studies have suggested a substantial heritable component. Our objective is to provide a comprehensive, genome-wide evaluation of inherited risks and possible mechanisms of etiology in BPH.We performed a three-stage, genome-wide association study (GWAS) of men from three independent populations, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, the CLUE II cohort, and a Finnish hospital-based population. DNA samples were genotyped using the Illumina HumanOmniExpress BeadChip in REDUCE and CLUE II, and using the Sequenom iPLEX system for the confirmation stage in the Finnish population. A logistic regression model was used to evaluate the association between each SNP and BPH/LUTS.Fourteen SNPs reached P?

SUBMITTER: Na R

PROVIDER: S-EPMC5565164 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).

Na Rong R Helfand Brian T BT Chen Haitao H Conran Carly A CA Crawford Susan E SE Hayward Simon W SW Tammela Teuvo L J TLJ Hoffman-Bolton Judy J Zheng Siqun L SL Walsh Patrick C PC Schleutker Johanna J Platz Elizabeth A EA Isaacs William B WB Xu Jianfeng J

The Prostate 20170628 11

<h4>Background</h4>Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common conditions. Little is known about their etiologies except that studies have suggested a substantial heritable component. Our objective is to provide a comprehensive, genome-wide evaluation of inherited risks and possible mechanisms of etiology in BPH.<h4>Methods</h4>We performed a three-stage, genome-wide association study (GWAS) of men from three independent populations, the REduc ...[more]

PMID: 28656603

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Project description: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-?2, were increased, and administration of anti-TGF-?2 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.

Dataset Information

A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).

Publications

A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).

Similar Datasets

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