Protein Biomarker Analysis of Primary Peyronie\u27s Disease Cells

Abstract

INTRODUCTION: The molecular pathogenesis of Peyronie\u27s Disease (PD) remains unclear more than 250 years after its initial description. Because of this, no test is currently available to accurately predict PD progression among those affected. AIM: To investigate the expression of wound healing and fibrosis-associated proteins in primary cell cultures of PD fibroblasts to determine whether altered protein expression patterns can be used as predictors of clinical course and natural history. METHODS: Primary cell cultures derived from normal Tunica albuginea tissue and PD plaque tissue were examined by immuno-cytochemistry. Protein expression profiles were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) and Western immunoblotting. MAIN OUTCOME MEASURES: Expression of wound healing and fibrosis-associated proteins and protein expression patterns were assessed. RESULTS: Statistically significant increases in smooth muscle alpha-actin, beta-catenin, and Heat shock proteins (Hsp47) were identified in cells derived from PD relative to cells derived from normal Tunica albuginea tissue. Changes in TGFbeta-1 receptor and Fibronectin were also observed. In addition, altered expression of additional as yet unidentified proteins at 4.7, 8.9, 10.8, 16.8, and 76.8 kDa were detected by complementary SELDI-TOF-MS approaches. CONCLUSIONS: Primary cells derived from PD plaques display up-regulated expression of several proteins that are established components of fibrosis and wound healing. In addition, changes in other, as yet unidentified proteins were measured. It will be of interest to conduct further studies to see whether these dysregulated protein peaks represent potential biological markers of disease progression