The Obstructed Bladder: Expression of Collagen, Matrix Metalloproteinases, Muscarinic Receptors, Angiogenic and Neurotrophic Factors in Patients with Benign Prostatic Hyperplasia

to evaluate gene expression of Collagen, Matrix Metalloproteinases (MMP) and Inhibitors, Cholinergic Muscarinic Receptors (CHRM), Angiogenic and Nerve Growth Factors (NGF) in the bladder of patients with Bladder Outlet Obstruction due to Benign Prostatic Hyperplasia METHODS: We analyzed bladder specimens from 43 patients with obstructive BPH undergoing TURP as compared to 10 age-matched controls with IPSS<8 and prostate <30g. A bladder biopsy was performed for relative gene expression analysis with qRT-PCR of Collagens I and III, MMPs 1,2,9; Tissue Inhibitors of Metalloproteinases (TIMP) 1,2 and RECK; CHRM2 and -3; VEGF, CD105; NGF and NGF receptor.

Patients with BOO presented statistically significant overexpression of Collagens I and III, VEGF, CHRM2 and CHRM3. CD105, MMP-9 and TIMP-1 were underexpressed. Expression of NGF, NGFr, MMP-1, MMP-2, TIMP-2 and RECK were heterogeneous. CHRM2 and CHRM3 were overexpressed in patients with persistent detrusor overactivity. Smokers presented upregulation of NGFr and VEGF; dyslipidemic patients had overexpression of NGFr.

Bladder upregulation of collagens I and III on transcriptional level appears to be relevant in BPH. Muscarinic receptors CHRM2 and CHRM3 are also overexpressed; more so in patients with persistent detrusor overactivity. Upregulation of VEGF and NGFr particularly in subjects with risk factors for atherosclerosis reinforce the role of ischemia in BPH-induced modifications of the bladder.

Urology. 2017 May 12 [Epub ahead of print]

João Arthur Brunhara Alves Barbosa, Sabrina T Reis, Marco Nunes, Yuri A Ferreira, Katia R Leite, William C Nahas, Miguel Srougi, Alberto A Antunes

University of Sao Paulo School of Medicine, Division of Urology. Electronic address: ., Laboratory of Investigative Urology, LIM55, University of Sao Paulo School of Medicine., University of Sao Paulo School of Medicine, Division of Urology., University of Sao Paulo School of Medicine, Division of Urology; Laboratory of Investigative Urology, LIM55, University of Sao Paulo School of Medicine.

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