Benign prostatic hyperplasia (BPH) is a widely prevalent age-associated disease that is the main contributor to lower urinary tract dysfunction (LUTD) in aging men. Although prostate fibrosis has been recognized as a contributor to BPH pathophysiology, there are not any clinically available therapeutics that target this aspect of disease progression. In this study, we evaluated the antifibrotic potential of thalidomide using both in vitro and in vivo models of BPH/LUTD. Using benign human prostate stromal cells stimulated with transforming growth factor β-1 (TGFβ1) followed by targeted transcriptomic profiling and assessment of canonical TGFβ signaling, we demonstrate that thalidomide attenuates expression of profibrotic genes, including extracellular matrix components. In aged male mice with LUTD, thalidomide administration led to a reduction in prostate collagen deposition and decreased organization of collagen fiber alignment. Functionally, thalidomide treatment improved LUTD in aged male mice, while prostate mass, androgen receptor expression and downstream signaling targets, and proliferative index remained unchanged, suggesting that the observed therapeutic effects are primarily mediated by antifibrotic mechanisms. Our findings highlight thalidomide's potential to modulate prostatic fibrosis and improve voiding function and support further investigation into the role of antifibrotic therapies as novel treatments for BPH/LUTD. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
The Journal of pathology. 2026 May 27 [Epub ahead of print]
Ajinkya R Limkar, Sophia M Vrba, Emily A Ricke, Zsuzsanna Fabry, Matthew S Lee, Kevin T McVary, William A Ricke
Department of Urology, George M. O'Brien Center for Research Excellence, University of Wisconsin Madison, Madison, WI, USA., Medical Scientist Training Program, University of Wisconsin Madison, Madison, WI, USA., Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI, USA., Department of Urology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA., Loyola University Stritch School of Medicine, Maywood, IL, USA.