Extracellular Matrix Alterations and the Antifibrotic Role of Mycophenolate Mofetil in a Model of Peyronie's Disease

Peyronie's disease (PD) is a fibrotic disorder of the tunica albuginea marked by extracellular matrix (ECM) remodeling, leading to penile curvature and erectile dysfunction. This study aimed to evaluate ECM alterations in a rat model of PD induced by transforming growth factor beta and to assess the potential antifibrotic effects of mycophenolate mofetil (MMF). Thirty male Wistar rats were divided into control, SHAM, PD (7 and 30 days), and PD+MMF-treated (7 and 30 days) groups (n=5/group). Histological and immunohistochemical analyses were performed in the tunica albuginea. PD induction resulted in an imbalance between total collagen and reticulin fibers, a hallmark of early fibrosis, and increased proteoglycan deposition and elastic fiber disorganization. These changes were more pronounced at 30 days post-induction. MMF treatment for 30 days significantly reduced collagen ratio, restored collagen organization, and normalized the distribution of elastic fibers. Proteoglycan levels, elevated in untreated PD animals, were also decreased after 30 days of MMF therapy. In addition, MMF modulated matrix metalloproteinase (MMP) expressions, notably enhancing MMP-2 and MMP-3 levels, and altered the balance of fibroblasts and myofibroblasts in a time-dependent manner. These findings suggest that MMF has antifibrotic effects and may be a promising therapeutic strategy for PD, particularly in the early stages of fibrosis:°.