Pentoxifylline attenuates transforming growth factor-β1-stimulated elastogenesis in human Tunica albuginea-derived fibroblasts part 2: Interference in a TGF-β1/smad-dependent mechanism and downregulation of AAT1

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

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Introduction. Transforming growth factor-beta1 (TGF-β1) contributes to the pathogenesis of Peyronie's disease (PD). Pentoxifylline (PTX) antagonizes the effects of TGF-β1 and has been utilized in our clinic for the management of PD although the mechanisms of action are not entirely clear. Aim.: We studied cell-signaling pathways through which TGF-β1 and PTX mediate collagen metabolism, elastin expression, 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.: Reverse-transcription polymerase chain reaction and Western blotting were utilized to assess differences in elastin metabolism and cellular signaling between groups. Alpha-1 antitrypin (AAT1) expression was assayed. Results.: At doses greater than 0.1 ng/Ml, TGF-β1 increased messenger ribonucleic acid (mRNA) and protein expression of elastin in a time-dependent fashion in TADF. PTX did not interfere with TGF-β1 mediated upregulation of elastin mRNA and protein in TADF. However, pretreatment of TADF with PTX was associated with decreased expression of AAT1, decreased activity of the Smad1/5 pathway, and enhanced phosphorylation of the inhibitory Smad6. Conclusion.: Expression of elastin mRNA and protein is upregulated in TADF by TGF-β1. PTX has no effect on elastin production but attenuates elastogenesis in TADF through an AAT1-related mechanism.

Original languageEnglish (US)
Pages (from-to)1787-1797
Number of pages11
JournalJournal of Sexual Medicine
Volume7
Issue number5
DOIs
StatePublished - 2010

Keywords

  • Alpha Antitrypsin
  • Elastin
  • Pentoxifylline
  • Peyronie's Disease
  • Smads
  • Tunica Albuginea

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Medicine(all)

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