Pentoxifylline Attenuates Transforming Growth Factor-β1-Stimulated Collagen Deposition and Elastogenesis in Human Tunica Albuginea-Derived Fibroblasts Part 1: Impact on Extracellular Matrix

Introduction. Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in the pathogenesis of Peyronie's disease (PD) and also plays a role in collagen and elastin metabolism. Pentoxifylline (PTX) antagonizes the effects of TGF-beta 1 and has been utilized in our clinic for the management of PD. Aim. We studied the effects of TGF-beta 1 and PTX on collagen metabolism and elastogenesis in tunica albuginea-derived fibroblasts (TADFs). Methods. TADFs from men with and without PD were cultured and treated with TGF-beta 1 and PTX as monotherapy at differing concentrations and time points. Combination treatment (TGF-beta 1 followed by PTX and vice versa) was also investigated. Main Outcome Measures. Cell proliferation assay, enzyme-linked immunosorbent assay, and immunohistochemistry were utilized to assess the impact of TGF-beta 1 and PTX on TADF with respect to elastin and collagen I metabolism. Results. PTX inhibited fibroblast proliferation at doses of 100 mu M. TGF-beta 1 stimulated elastogenesis and collagen I fiber deposition in TADF in a dose- and time-dependent fashion. Pretreatment with PTX dramatically attenuated TGF-beta 1-mediated elastogenesis and collagen fiber deposition in TADF from men with and without PD. Interestingly, production of collagen I was higher in untreated Peyronie's tunica (PT) cells relative to normal tunica (NT) cells; furthermore, PTX attenuated collagen production to levels similar to untreated control TADF in PT cells but not in NT cells, suggesting important intrinsic differences between PT and NT cells. Conclusion. Both elastin and collagen are upregulated by TGF-beta 1 in TADF. This likely contributes to the PD phenotype. Pretreatment with PTX attenuates both collagen fiber deposition and elastogenesis in TADF exposed to TGF-beta 1; these effects suggest a useful role for PTX in the management of PD. Shindel AW, Lin G, Ning H, Banie L, Huang Y-C, Liu G, Lin C-S, and Lue TF. Pentoxifylline attenuates TGF-beta 1 stimulated collagen deposition and elastogenesis in human tunica albuginea-derived fibroblasts Part 1: Impact on extracellular matrix. J Sex Med 2010;7:2077-2085.