Castro Patricia, Giri Dipak, Lamb Dolores, Ittmann Michael
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, 2002 Holcombe Boulevard, Houston, TX 77030, USA.
Prostate. 2003 Apr 1;55(1):30-8. doi: 10.1002/pros.10204.
Senescent cells accumulate in tissues with age and show changes in protein expression that may influence the function of adjacent cells and contribute to the development of tissue pathologies associated with aging. Benign prostatic hyperplasia (BPH) is an extremely common disease of older men characterized by increased growth of prostatic epithelial and stromal cells. In BPH, there is an increased expression of Il-1alpha by prostatic epithelial cells that results in elevated expression of FGF7 by stromal cells, which in turn is strongly correlated with epithelial proliferation.
Human BPH tissue and primary cultures of prostatic epithelial cells were analyzed by histochemical and quantitative assays for senescence-associated beta galactosidase (SA-beta gal). Il-1alpha expression was localized by immunohistochemistry and Il-1alpha tissue content determined by enzyme-linked immunoabsorption assay.
Expression of Il-1alpha is significantly increased in vitro when cultured prostatic epithelial cells undergo senescence. In BPH tissue a substantial population of epithelial cells express senescence-associated beta galactosidase (SA-beta gal), a marker of cellular senescence. By quantitative assay, SA-beta gal activity is correlated with both tissue levels of Il-1alpha and the severity of BPH.
One mechanism driving BPH in older men is the accumulation of senescent epithelial cells expressing Il-1alpha, which in turn increases FGF7 secretion and proliferation of non-senescent epithelial cells. Thus there is a mechanistic linkage between cellular senescence and one of the most common pathologies of older men.
衰老细胞会随着年龄增长在组织中积累，并表现出蛋白质表达的变化，这可能会影响相邻细胞的功能，并促使与衰老相关的组织病理学发展。良性前列腺增生（BPH）是老年男性极为常见的疾病，其特征是前列腺上皮细胞和基质细胞过度生长。在BPH中，前列腺上皮细胞中白细胞介素-1α（Il-1α）表达增加，导致基质细胞中FGF7表达升高，而这又与上皮细胞增殖密切相关。
通过组织化学和定量分析，对人BPH组织和前列腺上皮细胞原代培养物进行衰老相关β半乳糖苷酶（SA-βgal）检测。通过免疫组织化学定位Il-1α表达，并通过酶联免疫吸附测定法测定Il-1α组织含量。
当培养的前列腺上皮细胞衰老时，体外Il-1α表达显著增加。在BPH组织中，大量上皮细胞表达衰老相关β半乳糖苷酶（SA-βgal），这是细胞衰老的标志物。通过定量分析，SA-βgal活性与Il-1α的组织水平和BPH的严重程度相关。
老年男性BPH发生的一种机制是表达Il-1α的衰老上皮细胞积累，这反过来又增加了FGF7的分泌和非衰老上皮细胞的增殖。因此，细胞衰老与老年男性最常见的病理之一之间存在机制联系。
