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 language | English (US) |
|---|---|
| Pages (from-to) | 1787-1797 |
| Number of pages | 11 |
| Journal | Journal of Sexual Medicine |
| Volume | 7 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2010 |
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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 journal › Article
}
TY - JOUR
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
Y1 - 2010
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
UR - http://www.scopus.com/inward/record.url?scp=77953592469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953592469&partnerID=8YFLogxK
U2 - 10.1111/j.1743-6109.2010.01749.x
DO - 10.1111/j.1743-6109.2010.01749.x
M3 - Article
C2 - 20384945
AN - SCOPUS:77953592469
VL - 7
SP - 1787
EP - 1797
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
SN - 1743-6095
IS - 5
ER -