Watanabe Marcelo Silva, Theodoro Thérèse Rachel, Coelho Natália Lima, Mendes Aline, Leonel Monica Luzia Pereira, Mader Ana Maria, Nader Helena Bonciani, Glina Sidney, Pinhal Maria Aparecida Silva
Biochemistry Departament, Faculdade de Medicina do ABC, Santo André 09060-650, Brazil.
Biochemistry Department Universidade Federal de São Paulo, UNIFESP, São Paulo 04044-020, Brazil.
J Adv Res. 2017 Jul;8(4):455-461. doi: 10.1016/j.jare.2017.06.004. Epub 2017 Jun 15.
Peyronie's disease is characterized by fibrous plaque formation of the tunica albuginea, causing penile deformity and fertility problems. The aim of the present study was to investigate alterations in the extracellular matrix in Peyronie's disease. The study used tissues collected by surgical procedure from individuals that presented a well-established disease, while control samples were obtained by biopsies of fresh cadavers. Immunohistochemistry analysis followed by digital quantification was performed to evaluate TGF-β, heparanases and metalloproteinases (MMPs). The profile of sulfated glycosaminoglycans, chondroitin sulfate and dermatan sulfate was determined by agarose gel electrophoresis, while hyaluronic acid quantification was obtained by an ELISA-like assay. The expression of mRNA was investigated for syndecan-1 proteoglycan (Syn-1), interleukine-6 (IL-6), hyaluronic acid synthases, and hyaluronidases. Pathologic features showed decreased apoptosis and blood vessel number in Peyronie's tissues. TGF-β and IL-6 were significantly enhanced in Peyronie's disease. There was an increased expression of heparanases, though no alteration was observed for MMPs. Hyaluronic acid as well as hyaluronic acid synthases, hyaluronidases, and dermatan sulfate were not changed, while the level of chondroitin sulfate was significantly ( = 0.008, Mann-Whitney test) increased in Peyronie's samples. Heparanases and sulfated glycosaminoglycans seem to be involved in extracellular matrix alterations in Peyronie's disease.
佩罗尼氏病的特征是白膜形成纤维斑块，导致阴茎畸形和生育问题。本研究的目的是调查佩罗尼氏病细胞外基质的变化。该研究使用通过手术程序从患有确诊疾病的个体收集的组织，而对照样本则通过新鲜尸体活检获得。进行免疫组织化学分析并随后进行数字定量，以评估转化生长因子-β（TGF-β）、乙酰肝素酶和金属蛋白酶（MMPs）。通过琼脂糖凝胶电泳确定硫酸化糖胺聚糖、硫酸软骨素和硫酸皮肤素的概况，而透明质酸定量则通过类似酶联免疫吸附测定（ELISA）的方法获得。研究了syndecan-1蛋白聚糖（Syn-1）、白细胞介素-6（IL-6）、透明质酸合成酶和透明质酸酶的mRNA表达。病理特征显示佩罗尼氏病组织中的细胞凋亡和血管数量减少。TGF-β和IL-6在佩罗尼氏病中显著增强。乙酰肝素酶的表达增加，而MMPs未观察到变化。透明质酸以及透明质酸合成酶、透明质酸酶和硫酸皮肤素没有变化，而硫酸软骨素水平在佩罗尼氏病样本中显著升高（曼-惠特尼检验，P = 0.008）。乙酰肝素酶和硫酸化糖胺聚糖似乎参与了佩罗尼氏病的细胞外基质改变。
