OBJECTIVES Peyronie's disease (PD) is accompanied by remodelling of connective tissue into fibrotic plaque. Treatment of the inflammatory and fibrotic phases of the disease is not established. The aim of the study was to evaluate the effect of verapamil (VER) and bacterial collagenase (COLL) on collagen metabolism and cell migration in fibroblasts with experimental wound healing and inflammation as an in vitro model of PD. MATERIALS AND METHODS In vitro model of PD was designed using experimental model of inflammation induced by Interleukin-1 (IL-1) in cultured fibroblasts and mechanical damage of the cells. Cell viability, cell proliferation, collagen biosynthesis, prolidase activity and cell migration were studied in both models of the cells treated with VER and COLL. RESULTS VER decreased cell viability, DNA and collagen biosynthesis and increased prolidase activity in control fibroblast, while in "wounded" fibroblasts it significantly decreased all the processes. COLL did not affect cell viability and DNA biosynthesis, while inhibited collagen biosynthesis and prolidase activity in both control and "wounded" fibroblasts. In IL-1-treated fibroblasts VER inhibited all studied processes except prolidase activity, while COLL inhibited only collagen biosynthesis and prolidase activity. COLL accelerated cell migration, while VER attenuated the process in fibroblast model of wound healing, compared to control cells. CONCLUSION VER and COLL attenuate collagen biosynthesis in both fibroblast models. The VER-dependent inhibition of collagen biosynthesis was accompanied by inhibition of DNA biosynthesis at high prolidase activity, while COLL affected this process through inhibition of prolidase activity at high rate of DNA biosynthesis. It shows that anti-fibrotic activity of VER/COLL and anti-inflammatory activity of VER may represent approach to establish standard treatment of PD.

中文翻译：

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维拉帕米和胶原酶差异性影响Peyronie病实验模型中的胶原代谢。

目的佩罗尼氏病（PD）伴随着结缔组织重塑为纤维化斑块。该疾病的炎性和纤维化期的治疗尚未建立。该研究的目的是评估维拉帕米（VER）和细菌胶原酶（COLL）对成纤维细胞胶原代谢和细胞迁移的影响，并以实验性伤口愈合和炎症作为PD的体外模型。材料与方法采用体外培养的成纤维细胞中白介素-1（IL-1）诱导的炎症和细胞机械损伤的实验模型设计了PD的体外模型。在用VER和COLL处理的两种细胞模型中都研究了细胞活力，细胞增殖，胶原蛋白的生物合成，蛋白酶活性和细胞迁移。结果VER细胞活力降低，在对照成纤维细胞中，DNA和胶原蛋白的生物合成和脯氨酸酶活性增加，而在“受伤”成纤维细胞中，它显着减少了所有过程。COLL不影响细胞活力和DNA生物合成，而在对照和“受伤”成纤维细胞中均抑制胶原生物合成和脯氨酸酶活性。在经IL-1处理的成纤维细胞中，VER抑制了蛋白水解酶活性以外的所有研究过程，而COLL仅抑制了胶原的生物合成和蛋白水解酶活性。与对照细胞相比，COLL可加速细胞迁移，而VER可减轻创面成纤维细胞模型伤口愈合的过程。结论VER和COLL减弱了两种成纤维细胞模型中胶原的生物合成。VER依赖性的胶原蛋白生物合成抑制作用伴随着高蛋白水解酶活性对DNA生物合成的抑制作用，而COLL通过以高DNA生物合成速率抑制脯氨酸酶活性来影响这一过程。这表明VER / COLL的抗纤维化活性和VER的抗炎活性可能代表建立PD的标准治疗方法。