Pentoxifylline attenuates transforming growth factor-β1-stimulated collagen deposition and elastogenesis in human tunica albuginea-derived fibroblasts part 1: Impact on extracellular matrix

Alan W. Shindel, Guiting Lin, Hongxiu Ning, Lia Banie, Yun Ching Huang, Gang Liu, Ching Shwun Lin, Tom F. Lue

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Introduction.: Transforming growth factor-β1 (TGF-β1) 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-β1 and has been utilized in our clinic for the management of PD. Aim.: We studied the effects of TGF-β1 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-β1 and PTX as monotherapy at differing concentrations and time points. Combination treatment (TGF-β1 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-β1 and PTX on TADF with respect to elastin and collagen I metabolism. Results.: PTX inhibited fibroblast proliferation at doses of 100 μM. TGF-β1 stimulated elastogenesis and collagen I fiber deposition in TADF in a dose- and time-dependent fashion. Pretreatment with PTX dramatically attenuated TGF-β1-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-β1 in TADF. This likely contributes to the PD phenotype. Pretreatment with PTX attenuates both collagen fiber deposition and elastogenesis in TADF exposed to TGF-β1; these effects suggest a useful role for PTX in the management of PD.

Original languageEnglish (US)
Pages (from-to)2077-2085
Number of pages9
JournalJournal of Sexual Medicine
Volume7
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Elastin
  • Fibroblasts
  • Pentoxifylline
  • Peyronie's Disease
  • TGF-Beta
  • Tunica Albuginea

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynecology
  • Reproductive Medicine

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