This application from the University of Pittsburgh Planning Center for Interdisciplinary Research in Benign Urology (IR-BU) is proposed to study """"""""Molecular signatures associated with prostatic inflammation and antiinflammation in rodents and humans"""""""". Through the proposed multidisciplinary project, a team of investigators with different expertise including endocrinology, pathology, urology, and pharmacology will work together to determine similarities and dissimilarities in inflammation-induced gene expression changes between rodent and human prostates. We will particularly assay the impact of inflammation on the endocrine (i.e. androgens) and paracrine (i.e. cytokines and TGF-beta) signaling pathways given their established or implicated roles in BPH pathogenesis. The research hypothesis is that inflammation exerts similar effects in rodents and humans on androgen responsive genes and the levels and downstream targets of inflammatory cytokines and TGF-beta. Capsaicin-induced acute and bacterial infection-induced chronic inflammation in the rat prostate will be used as models. We will compare inflammation-associated alterations in androgen-responsive gene expression (Specific Aim 1), inflammatory responses (Specific Aim 2), and TGF-beta signaling (Specific Aim 3) in the rodent and human prostates. The success of this research project will identify relevant targets and signaling pathways in rodents that respond to inflammation to generate altered prostate tissue homeostasis characteristic of BPH in humans. The IR-BU has established an Administrative Core, which includes an Executive Committee and an Internal Advisory Committee, will provide strong administrative support through project review, promoting collaborations, and educational enrichment. The Core will also be responsible for allocation and oversight of IR-BU resources. Through supporting the educational enrichment and research project, the Administrative Core will help to both integrate the IR-BU into the University community by serving as a resource and to attract new investigators to the field of BPH.

Public Health Relevance

Benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) is a major medical problem affecting most elderly men and costing society ~$4 billion annually. Success of the proposed multidisciplinary research will facilitate further analysis of the molecular mechanisms of BPH.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory Grants (P20)
Project #
5P20DK090919-02
Application #
8151009
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (O1))
Program Officer
Hoshizaki, Deborah K
Project Start
2010-09-30
Project End
2012-08-31
Budget Start
2011-08-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$149,985
Indirect Cost
Name
University of Pittsburgh
Department
Urology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Funahashi, Yasuhito; Wang, Zhou; O'Malley, Katherine J et al. (2015) Influence of E. coli-induced prostatic inflammation on expression of androgen-responsive genes and transforming growth factor beta 1 cascade genes in rats. Prostate 75:381-9
Sugino, Yoshio; O'Malley, Katherine J; Wang, Zhou et al. (2015) Laser-capture microdissection for analysis of cell type-specific gene expression of muscarinic receptor subtypes in the rat bladder with cyclophosphamide-induced cystitis. Int Urol Nephrol 47:637-42
Tyagi, Pradeep; Motley, Saundra S; Kashyap, Mahendra et al. (2015) Urine chemokines indicate pathogenic association of obesity with BPH/LUTS. Int Urol Nephrol 47:1051-8
Kashyap, Mahendra; Pore, Subrata; Wang, Zhou et al. (2015) Inflammasomes are important mediators of prostatic inflammation associated with BPH. J Inflamm (Lond) 12:37
O'Malley, Katherine J; Eisermann, Kurtis; Pascal, Laura E et al. (2014) Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia. Prostate 74:892-900
Funahashi, Yasuhito; O'Malley, Katherine J; Kawamorita, Naoki et al. (2014) Upregulation of androgen-responsive genes and transforming growth factor-?1 cascade genes in a rat model of non-bacterial prostatic inflammation. Prostate 74:337-45
Furuta, Akira; Suzuki, Yasuyuki; Honda, Mariko et al. (2012) Time-dependent changes in bladder function and plantar sensitivity in a rat model of fibromyalgia syndrome induced by hydrochloric acid injection into the gluteus. BJU Int 109:306-10
Honda, Masashi; Takenaka, Atsushi; Inoue, Seiya et al. (2012) Sensory neurone-specific receptor-mediated regulation of micturition reflex in urethane-anaesthetized rats. BJU Int 109:628-33
Chuang, Yao-Chi; Yoshimura, Naoki; Huang, Chao-Cheng et al. (2010) Expression of E-series prostaglandin (EP) receptors and urodynamic effects of an EP4 receptor antagonist on cyclophosphamide-induced overactive bladder in rats. BJU Int 106:1782-7