This competing renewal 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 in rodent models"""""""". Because of the importance of inflammation in BPH, a team of investigators with different expertise including endocrinology, pathology, urology, and pharmacology will work together to determine similarities and dissimilarities in inflammation-induced molecular and cellular changes in and/or outside the prostate between rodents and humans in this multidisciplinary project. The research hypothesis is that prostatic inflammation can induce molecular and cellular changes associated with human BPH. This hypothesis is supported by the finding during the current funding period that formalin-induced low grade inflammation enhanced expression of androgen-responsive genes in the formalin-injection rat prostate model and our previous finding that androgen-responsive gene expression is elevated in human BPH epithelial cells. Using formalin-induced rat prostate inflammation as a model, we propose to determine the effect of prostatic inflammation on bladder and afferent function (Specific Aim 1), inflammatory cytokine profile in the prostate and urine (Specific Aim 2), and prostatic epithelial-mesenchymal transition (Specific Aim 3). 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.
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 and cellular mechanisms of BPH and related LUTS, which may lead to novel preventive and/or therapeutic approaches for this disease.
|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|