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

Abstract

To evaluate the gene expression of collagen, matrix metalloproteinases (MMPs) and inhibitors, cholinergic muscarinic receptors (CHRMs), and angiogenic and nerve growth factors (NGFs) in the bladder of patients with bladder outlet obstruction caused by benign prostatic hyperplasia (BPH). We analyzed bladder specimens from 43 patients with obstructive BPH undergoing transurethral resection of the prostate as compared to 10 age-matched controls with an International Prostatic Symptom Score of <8 and a prostate volume of <30 g. A bladder biopsy was performed for relative gene expression analysis with quantitative real-time polymerase chain reaction of collagens I and III, MMP-1, MMP-2, and MMP-9; tissue inhibitors of metalloproteinases (TIMPs) TIMP-1, TIMP-2, and reversion-inducing cysteine-rich protein with kazal motifs (RECK); CHRM2 and CHRM3; VEGF and CD105; and NGF and nerve growth factor receptor (NGFr). Patients with bladder outlet obstruction presented a statistically significant overexpression of collagens I and III, VEGF, CHRM2, and CHRM3. CD105, MMP-9, and TIMP-1 were underexpressed. Expressions 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 an upregulation of NGFr and VEGF; dyslipidemic patients had an 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, reinforces the role of ischemia in BPH-induced modifications of the bladder.