Alterations in the Transforming Growth Factor (TGF)-β Pathway as a Potential Factor in the Pathogenesis of Peyronie’s Disease

Haag, Simone M.; Hauck, Ekkehard W.; Szardening-Kirchner, Carolin; Diemer, Thorsten; Cha, Eun-Sook; Weidner, W.; Eickelberg, Oliver

doi:10.1016/j.eururo.2006.05.002

Cited by 72 publications

(46 citation statements)

References 16 publications

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“…5 Accumulating evidence suggests that transforming growth factor-b1 (TGF-b1) is one of the most relevant fibrogenic cytokines associated with PD. [6][7][8] The expression and activity of TGFb1 and its downstream signaling cascade, such as Smad2 and Smad3 transcription factors, have been shown to be increased in human PD plaque. 7,8 Moreover, we recently reported that a small-molecule inhibitor of activin receptor-like kinase 5, a TGF-b type I receptor, attenuated fibrotic responses in both a rat model of PD in vivo 9 and in fibroblasts isolated from human PD plaque in vitro.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8] The expression and activity of TGFb1 and its downstream signaling cascade, such as Smad2 and Smad3 transcription factors, have been shown to be increased in human PD plaque. 7,8 Moreover, we recently reported that a small-molecule inhibitor of activin receptor-like kinase 5, a TGF-b type I receptor, attenuated fibrotic responses in both a rat model of PD in vivo 9 and in fibroblasts isolated from human PD plaque in vitro. 8 Epigenetic modifications, such as histone acetylation/deacetylation, have been shown to play a role in both the pathogenesis of fibrotic disease and inflammatory disorders.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of histone deacetylase 2 mitigates profibrotic TGF-β1 responses in fibroblasts derived from Peyronie's plaque

Ryu¹,

Kim²,

Choi³

et al. 2013

Asian J Androl

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Epigenetic modifications, such as histone acetylation/deacetylation, have been shown to play a role in the pathogenesis of fibrotic disease. Peyronie's disease (PD) is a localized fibrotic process of the tunica albuginea, which leads to penile deformity. This study was undertaken to determine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of histone deacetylase 2 (HDAC2) in primary fibroblasts derived from human PD plaque. PD fibroblasts were pre-treated with HDAC2 siRNA and then stimulated with transforming growth factor-b1 (TGF-b1). Protein was extracted from treated fibroblasts for Western blotting and the membranes were probed with antibody to phospho-Smad2/Smad2, phospho-Smad3/Smad3, smooth muscle a-actin and extracellular matrix proteins, including plasminogen activator inhibitor-1, fibronectin, collagen I and collagen IV. We also performed immunocytochemistry to detect the expression of extracellular matrix proteins and to examine the effect of HDAC2 siRNA on the TGF-b1-induced nuclear translocation of Smad2/3 in fibroblasts. Knockdown of HDAC2 in PD fibroblasts abrogated TGF-b1-induced extracellular matrix production by blocking TGF-b1-induced phosphorylation and nuclear translocation of Smad2 and Smad3, and by inhibiting TGF-b1-induced transdifferentiation of fibroblasts into myofibroblasts. Decoding the individual function of the HDAC isoforms by use of siRNA technology, preferably siRNA for HDAC2, may lead to the development of specific and safe epigenetic therapies for PD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of histone deacetylase 2 mitigates profibrotic TGF-β1 responses in fibroblasts derived from Peyronie's plaque

Ryu¹,

Kim²,

Choi³

et al. 2013

Asian J Androl

View full text Add to dashboard Cite

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“…Alterations in the TGF-b pathway appear to be a pathogenetic factor in the development of PD. 7 It has been demonstrated that TGF-b1 downregulates the expression levels and activity of antioxidant enzymes, including glutathione S-transferase, glutamate-cysteine ligase, superoxide dismutase and glutathione peroxidase. 34,35 TGF-b1 inhibits antioxidant enzyme expression through Smad3/ATFdependent Nrf2 inactivation.…”

Section: Discussionmentioning

confidence: 99%

“…However, in recent years, increased expression of transforming growth factor (TGF)-b1 in fibrotic plaques of patients with PD has been described. 7 Furthermore, an increase in oxidative stress has been postulated as potentially damaging for the tunica albuginea in acute phase of the disease. 8 Coenzyme Q 10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone, CoQ 10 ) is a fat-soluble, vitamin-like quinone commonly known as ubiquinone or ubidecarenone.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of coenzyme Q10 supplementation in early chronic Peyronie's disease: a double-blind, placebo-controlled randomized study

Safarinejad¹

2010

Int J Impot Res

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“…The etiology of PD is not fully understood, although in recent years new studies propose the penile trauma as cause of PD [3]. A recent hypothesis suggests that the replicative/tumor-like nature of PD should be regarded as similar to that of keloids [4][5][6][7][8].The disease may occur as a result of traumas or injuries to the penis usually during sexual activity, although the majority of PD-patients do not remember a traumatic event.…”

Section: Introductionmentioning

confidence: 99%

Pentoxifylline Associated with Other Antioxidants (Multimodal Therapy) on Patients with Peyronie's Disease. Results of a Controlled Study

Paulis¹,

Farina²,

Cavallini³

et al. 2014

Andrology(Los Angel)

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Objective: The study was made mainly to investigate the possible benefits of multimodal treatment using Pentoxifylline (PTX) with other antioxidants, in patients with PD enrolled for a conservative medical management. Methods: We carried out a controlled study on 240 patients diagnosed with Peyronie's Disease (PD). We have divided two treatment groups, which differ from each other only for the association with PTX-penile injection. Two groups (A and B) were totally composed by 160 PD patients (80 patients for each group): Group A=PTX injection (penile and peri-lesional) 100 mg, every two weeks for six months + PTX 400 mg /oral/ twice daily + propolis 600 mg / oral / daily + blueberries 160 mg /oral/ daily + Vitamin E 600 mg / oral / daily + topical Diclofenac sodium 4% gel / twice a day, for a period of 6 months. Group B=the same therapy of group A but without PTX penile injection. Patients who refused treatment, for various reasons, were included in the control group=Group C (80 patients). Results: In groups A and B after 6 months of treatment a reduction of penile plaque volume of 50.3% and 25.9% respectively was observed, while in group C a mean increase in plaque volume of 131% was observed. Furthermore, in groups A and B, the mean curvature decrease was -11.07° and -4.4° respectively, while in group C a mean increase of curvature =+14.09° was observed. Conclusion: Our results showed that multimodal treatment with PTX associated with antioxidants and topical Diclofenac is significantly effective in treating PD. Treatment outcomes obtained in the treatment-group A are statistically more significant than those achieved in group B. Pentoxifylline is more effective when the treatment program includes both routes of administration: oral + perilesional injection.

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Alterations in the Transforming Growth Factor (TGF)-β Pathway as a Potential Factor in the Pathogenesis of Peyronie’s Disease

Cited by 72 publications

References 16 publications

Inhibition of histone deacetylase 2 mitigates profibrotic TGF-β1 responses in fibroblasts derived from Peyronie's plaque

Inhibition of histone deacetylase 2 mitigates profibrotic TGF-β1 responses in fibroblasts derived from Peyronie's plaque

Safety and efficacy of coenzyme Q10 supplementation in early chronic Peyronie's disease: a double-blind, placebo-controlled randomized study

Pentoxifylline Associated with Other Antioxidants (Multimodal Therapy) on Patients with Peyronie's Disease. Results of a Controlled Study

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