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


OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Shindel
Alan W
AW
University of California-Knuppe Molecular Urology Laboratory, Department of Urology, San Francisco, CA, USA. Electronic address: shindela@urology.ucsf.edu.
Lin
Guiting
G
University of California-Knuppe Molecular Urology Laboratory, Department of Urology, San Francisco, CA, USA.
Ning
Hongxiu
H
University of California-Knuppe Molecular Urology Laboratory, Department of Urology, San Francisco, CA, USA.
Banie
Lia
L
University of California-Knuppe Molecular Urology Laboratory, Department of Urology, San Francisco, CA, USA.
Huang
Yun-Ching
YC
University of California-Knuppe Molecular Urology Laboratory, Department of Urology, San Francisco, CA, USA.
Liu
Gang
G
University of California-Knuppe Molecular Urology Laboratory, Department of Urology, San Francisco, CA, USA.
Lin
Ching-Shwun
CS
University of California-Knuppe Molecular Urology Laboratory, Department of Urology, San Francisco, CA, USA.
Lue
Tom F
TF
University of California-Knuppe Molecular Urology Laboratory, Department of Urology, San Francisco, CA, USA.
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism*; D004547:Elastic Tissue / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008856:Microscopy, Fluorescence; D010411:Penile Induration / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D010413:Penis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000502:physiology*
D024042:Collagen Type I; D010726:Phosphodiesterase Inhibitors; D053773:Transforming Growth Factor beta1; D010431:Pentoxifylline