Haag Simone M, Hauck Ekkehard W, Eickelberg Oliver, Szardening-Kirchner Carolin, Diemer Thorsten, Weidner Wolfgang
Department of Urology and Pediatric Urology, Justus Liebig University Giessen, Giessen, Germany.
Eur Urol. 2008 Feb;53(2):425-30. doi: 10.1016/j.eururo.2007.06.036. Epub 2007 Jun 27.
A broad spectrum of options is available for treatment of Peyronie's disease; however, the effects of minimally invasive therapy are generally inadequate. Although useful, oral drugs must be administered at onset of the disease. Only a few patients request penile surgery. Therefore, new medical treatments for Peyronie's disease are needed. A better understanding of the pathogenesis of Peyronie's disease is required to facilitate development of these new medical treatments. Several studies have described an increased level of TGF-beta in the fibrotic plaques of patients with Peyronie's disease, underscoring this important signalling pathway in the onset and/or development of Peyronie's disease.
Plaque biopsies were taken from 16 patients with Peyronie's disease. Furthermore, 7 patients without Peyronie's disease were biopsied to provide control material. Fibroblasts were cultured from biopsy tissue, and cultured fibroblasts were stimulated with TGF-beta1, BMP-2, IFN-gamma, and IFN-gamma combined with one of the other stimuli. Protein was extracted from treated fibroblasts and prepared for immunoblots. The membranes were probed for phosphorylated Smad and total Smad to indicate activation of TGF-beta signalling.
An agonistic effect of IFN-gamma on TGF-beta signalling was observed. Stimulation with TGF-beta1 increased levels of phospho-Smad2 and phospho-Smad3. After stimulation with TGF-beta1 and IFN-gamma combined, the levels of phospho-Smads were higher than those observed with stimulation withTGF-beta1 alone.
The profibrotic effect of TGF-beta1 is enhanced by IFN-gamma in fibroblasts from patients with Peyronie's disease. The inhibitory effects of IFN-gamma on the TGF-beta pathway do not appear in Peyronie's disease. Therefore, IFN-gamma cannot be taken as a useful tool in the therapy of Peyronie's disease.
治疗佩罗尼氏病有多种选择；然而，微创治疗的效果通常并不理想。口服药物虽有用，但必须在疾病发作时给药。只有少数患者要求进行阴茎手术。因此，需要针对佩罗尼氏病的新的医学治疗方法。为了促进这些新的医学治疗方法的开发，需要更好地了解佩罗尼氏病的发病机制。多项研究表明，佩罗尼氏病患者纤维化斑块中转化生长因子-β（TGF-β）水平升高，这突出了该重要信号通路在佩罗尼氏病发病和/或发展中的作用。
对16例佩罗尼氏病患者进行斑块活检。此外，对7例无佩罗尼氏病的患者进行活检以提供对照材料。从活检组织中培养成纤维细胞，并用TGF-β1、骨形态发生蛋白-2（BMP-2）、γ干扰素（IFN-γ）以及IFN-γ与其他刺激物之一联合刺激培养的成纤维细胞。从处理后的成纤维细胞中提取蛋白质并准备进行免疫印迹。用磷酸化Smad和总Smad对膜进行检测，以指示TGF-β信号通路的激活。
观察到IFN-γ对TGF-β信号通路有激动作用。用TGF-β1刺激可增加磷酸化Smad2和磷酸化Smad3的水平。在用TGF-β1和IFN-γ联合刺激后，磷酸化Smads的水平高于单独用TGF-β1刺激时观察到的水平。
在佩罗尼氏病患者的成纤维细胞中，IFN-γ增强了TGF-β1的促纤维化作用。在佩罗尼氏病中未出现IFN-γ对TGF-β通路的抑制作用。因此，IFN-γ不能作为治疗佩罗尼氏病的有效工具。
