Mulhall J P, Nicholson B, Pierpaoli S, Lubrano T, Shankey T V
Andrology Research Laboratory, VA Medical Center, Hines, USA.
Int J Impot Res. 2004 Jun;16(3):288-93. doi: 10.1038/sj.ijir.3901170.
Peyronie's disease is a fibrotic disorder, a condition characterized by cellular proliferation and excess extracellular matrix production. Previous work in related conditions has demonstrated chromosomal instability. This investigation was undertaken to analyze fibroblasts derived from Peyronie's disease tunical tissue for abnormalities of chromosome number and progression of cytogenetic aberrations during cell culture. Tunical tissue was excised from men with Peyronie's disease from both plaque and nonplaque tissue and cells were explanted in culture. Control cells were derived from both neonatal foreskins and normal tunica from men with congenital penile curvature. Fluorescent in situ hybridization was used to probe for chromosomes 7, 8, 17, 18, X and Y. Control cells demonstrated normal copy number for all chromosomes analyzed. In contrast, Peyronie's disease plaque-derived fibroblasts demonstrated frequent aneusomies in chromosomes 7, 8, 17, 18 and X and recurrent deletions of chromosome Y. Peyronie's disease nonplaque tunica-derived fibroblasts demonstrated infrequent chromosomal changes early in culture; however, with repeated passaging the majority of cell cultures demonstrated aneusomies in at least one chromosome. These data indicate that Peyronie's disease plaque-derived fibroblasts have consistent aneusomies even at early passage and that nonplaque tunica-derived cells from men with Peyronie's disease also demonstrate chromosomal instability. This suggests that the tunica albuginea of men with Peyronie's disease may be predisposed to undergoing unregulated fibrosis. These findings confirm the transformed nature of the Peyronie's disease tunical fibroblasts studied in this analysis. While the etiology of these findings is not clear, it is likely that these pathobiological characteristics contribute to the pathophysiology of this disease process.
佩罗尼氏病是一种纤维化疾病,其特征为细胞增殖和细胞外基质过度产生。先前在相关病症中的研究已证明染色体不稳定。本研究旨在分析源自佩罗尼氏病白膜组织的成纤维细胞的染色体数目异常以及细胞培养过程中细胞遗传学畸变的进展情况。从患有佩罗尼氏病的男性的斑块和非斑块组织中切除白膜组织,并将细胞接种于培养物中。对照细胞源自新生儿包皮以及患有先天性阴茎弯曲的男性的正常白膜。使用荧光原位杂交技术检测7号、8号、17号、18号染色体、X染色体和Y染色体。对照细胞在所分析的所有染色体上均显示正常拷贝数。相比之下,源自佩罗尼氏病斑块的成纤维细胞在7号、8号、17号、18号染色体和X染色体上频繁出现非整倍体,Y染色体则反复出现缺失。源自佩罗尼氏病非斑块白膜的成纤维细胞在培养早期显示出罕见的染色体变化;然而,随着传代次数的增加,大多数细胞培养物在至少一条染色体上出现了非整倍体。这些数据表明,即使在早期传代时,源自佩罗尼氏病斑块的成纤维细胞也存在一致的非整倍体,并且患有佩罗尼氏病的男性的非斑块白膜来源的细胞也表现出染色体不稳定。这表明患有佩罗尼氏病的男性的白膜可能易于发生不受控制的纤维化。这些发现证实了本分析中所研究的佩罗尼氏病白膜成纤维细胞的转化性质。虽然这些发现的病因尚不清楚,但这些病理生物学特征可能促成了该疾病过程的病理生理学。