Stromal Remodeling and Collagen Dynamics under Antifibrotic Conditions in the Rat Prostate

The prostate is a hormone-sensitive gland, in which stromal composition is important for epithelial regulation. Fibrotic alterations in the stroma may enhance epithelial imbalance and pre-neoplastic lesions. The purpose of this study was to assess the time-dependent antifibrotic effects of mycophenolate mofetil (MMF) in rat prostate. Male Wistar rats were treated with MMF for 7 or 30 days, and prostate samples were histologically and immunohistochemically examined. Stromal fiber content, hormone receptor expression, and immune cell incidence were analyzed. Collagen III and elastin fibers decreased at 7 days, with increased matrix metalloproteinases 2 expression and reduced androgen receptor in the epithelium, resulting in decreased proliferation and enhanced apoptosis. Collagen I breakdown at 30 days was associated with increased matrix metalloproteinases 13 and reduced smooth muscle area, with increased non-muscular stroma and vascular density. Degranulated mast cells were increased early on, and macrophages at 30 days, reflecting their successive involvement in stromal remodeling. These findings define two time windows of MMF-induced remodeling: initial extracellular matrix disassembly with epithelial influence, and later structural reorganization with vascular and immune components. This study provides relevant information about MMF as a potential tool for the study of antifibrotic response and stroma-epithelium interactions in androgen-dependent organs.