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

34 Citations (Scopus)

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

Fingerprint

Transforming Growth Factor beta1
Pentoxifylline
Transforming Growth Factors
Elastin
Down-Regulation
Fibroblasts
Penile Induration
RNA
Proteins
Fibroblast Growth Factors
Reverse Transcription
Up-Regulation
Collagen
Western Blotting
Phosphorylation
Outcome Assessment (Health Care)
Polymerase Chain Reaction

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Journal of Sexual Medicine, Vol. 7, No. 5, 2010, p. 1787-1797.

Research output: Contribution to journalArticle

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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.",
keywords = "Alpha Antitrypsin, Elastin, Pentoxifylline, Peyronie's Disease, Smads, Tunica Albuginea",
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T1 - Pentoxifylline attenuates transforming growth factor-β1-stimulated elastogenesis in human Tunica albuginea-derived fibroblasts part 2

T2 - Interference in a TGF-β1/smad-dependent mechanism and downregulation of AAT1

AU - Lin, Guiting

AU - Shindel, Alan W

AU - Banie, Lia

AU - Ning, Hongxiu

AU - Huang, Yun Ching

AU - Liu, Gang

AU - Lin, Ching Shwun

AU - Lue, Tom F.

PY - 2010

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N2 - 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.

AB - 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.

KW - Alpha Antitrypsin

KW - Elastin

KW - Pentoxifylline

KW - Peyronie's Disease

KW - Smads

KW - Tunica Albuginea

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