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• W1886559851 abstract "Transforming growth factor-beta1 (TGF-beta1) contributes to the pathogenesis of Peyronie's disease (PD). Pentoxifylline (PTX) antagonizes the effects of TGF-beta1 and has been utilized in our clinic for the management of PD although the mechanisms of action are not entirely clear.We studied cell-signaling pathways through which TGF-beta1 and PTX mediate collagen metabolism, elastin expression, and elastogenesis in tunica albuginea-derived fibroblasts (TADFs).TADFs from men with and without PD were cultured and treated with TGF-beta1 and PTX as monotherapy at differing concentrations and time points. Combination treatment (TGF-beta1 followed by PTX and vice versa) was also investigated.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.At doses greater than 0.1 ng/Ml, TGF-beta1 increased messenger ribonucleic acid (mRNA) and protein expression of elastin in a time-dependent fashion in TADF. PTX did not interfere with TGF-beta1 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.Expression of elastin mRNA and protein is upregulated in TADF by TGF-beta1. PTX has no effect on elastin production but attenuates elastogenesis in TADF through an AAT1-related mechanism." @default.
• W1886559851 created "2016-06-24" @default.
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• W1886559851 date "2010-05-01" @default.
• W1886559851 modified "2023-09-28" @default.
• W1886559851 title "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" @default.
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• W1886559851 doi "https://doi.org/10.1111/j.1743-6109.2010.01749.x" @default.
• W1886559851 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3163605" @default.
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