Hyperplasia and apoptosis. Opposing cellular processes that regulate the response of the rabbit bladder to transient outlet obstruction.
Hyperplasia and apoptosis. Opposing cellular processes that regulate the response of the rabbit bladder to transient outlet obstruction.
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发表时间：
1994-04
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通讯作者：
R. Santarosa;M. Colombel;S. Kaplan;F. Monson;R. Levin;R. Buttyan
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作者：
R. Santarosa;M. Colombel;S. Kaplan;F. Monson;R. Levin;R. Buttyan
背景兔尿道部分梗阻可诱导膀胱快速生长。这种生长的特征是平滑肌细胞肥大以及尿道鞘和浆膜中的细胞增生。已经提出生长因子的局部合成在这种生长中是有影响的，因为部分出口梗阻快速增加膀胱的碱性成纤维细胞生长因子的表达，同时抑制转化生长因子-β的表达。一旦出口梗阻解除，肥大的膀胱恢复到正常重量。在这里，我们研究是否回归的肥大兔膀胱涉及凋亡（程序性细胞死亡）的特定细胞元素和生长因子的表达是否改变伴随着凋亡细胞的删除。实验设计：分析退变兔膀胱的细胞凋亡标志物，包括DNA片段化和组织学。原位酶促免疫组织化学方法被用来定位这些组织中的凋亡细胞。最后，北方印迹分析用于鉴定膀胱退化期间碱性成纤维细胞生长因子和转化生长因子-β表达的变化。结果兔膀胱退变过程中出现典型的凋亡相关DNA片段的“梯状”电泳图谱。原位技术，以区分细胞与降解的核DNA确定的细胞凋亡，仅在膀胱尿道和servellament板的退化。与来自肥大膀胱的RNA相比，从退化膀胱提取的RNA表现出碱性成纤维细胞生长因子mRNA的表达降低以及转化生长因子-β 1 mRNA的表达增加。结论：我们的结论是，增生和凋亡是介导膀胱对短期梗阻性刺激的反应的相反的细胞过程，并且生长促进和生长抑制因子的局部合成可能负责启动这两种反应。
BACKGROUND Partial obstruction of the rabbit urethra induces rapid bladder growth. This growth is characterized by hypertrophy of smooth muscle cells in addition to hyperplasia of cells in the urothelium and serosa. The local synthesis of growth factors has been proposed to be influential in this growth since partial outlet obstruction rapidly increases the bladder's expression of basic fibroblast growth factor, while suppressing the expression of transforming growth factor-beta. Upon release of the outlet obstruction, the hypertrophied bladder regresses to its normal weight. Here, we examined whether regression of the hypertrophied rabbit bladder involves apoptosis (programmed cell death) of specific cellular elements and whether the expression of growth factors is altered concomitant with apoptotic cell deletion. EXPERIMENTAL DESIGN Regressing rabbit bladders were analyzed for markers of apoptosis, including DNA fragmentation and histology. An in situ enzymatic immuno-histochemical procedure was utilized to localize apoptotic cells in these tissues. Finally, Northern blot analysis was used to identify changes in the expression of basic fibroblast growth factor and transforming growth factor-beta during bladder regression. RESULTS Regressing rabbit bladders demonstrated the characteristic electrophoretic "ladder" pattern of DNA fragmentation associated with apoptosis. An in situ technique to distinguish cells with degraded nuclear DNA identified apoptosis only within the urothelium and serosal lamina of the regressing bladders. RNAs extracted from regressing bladders exhibited decreased expression of basic fibroblast growth factor mRNA as well as increased expression of transforming growth factor-beta 1 mRNA when compared with RNAs from hypertrophied bladders. CONCLUSIONS We conclude that hyperplasia and apoptosis are opposing cellular processes that mediate the bladder's response to short-term obstructive stimuli and that local synthesis of growth-promoting and growth-inhibitory factors may be responsible for initiating both of these responses.