Winyard P J, Nauta J, Lirenman D S, Hardman P, Sams V R, Risdon R A, Woolf A S
Developmental biology Unit, Institute of Child Health, London, England, United Kingdom.
Kidney Int. 1996 Jan;49(1):135-46. doi: 10.1038/ki.1996.18.
Various aberrations of cell biology have been reported in polycystic kidney diseases and in cystic renal dysplasias. A common theme in these disorders is failure of maturation of renal cells which superficially resemble embryonic tissue. Apoptosis is a feature of normal murine nephrogenesis, where it has been implicated in morphogenesis, and fulminant apoptosis occurs in the small, cystic kidneys which develop in mice with null mutations of bcl-2. Therefore, we examined the location and extent of apoptosis in pre- and postnatal samples of human polycystic and dysplastic kidney diseases using propidium iodide staining, in situ end-labeling and electron microscopy. In dysplastic kidneys cell death was prominent in undifferentiated cells around dysplastic tubules and was occasionally found in cystic epithelia. The incidence of apoptosis was significantly greater than in normal controls of comparable age both pre- and postnatally. In the polycystic kidneys there was widespread apoptosis in the interstitium around undilated tubules distant from cysts, in undilated tubules between cysts and in cystic epithelia. The level of apoptosis compared to controls was significantly increased postnatally. A similar increase of cell death was also noted in the early and late stages of renal disease in the polycystic cpk/cpk mouse model. We speculate that deregulation of cell survival in these kidneys may reflect incomplete tissue maturation, and may contribute to the progressive destruction of functional kidney tissue in polycystic kidneys and the spontaneous involution reported in cystic dysplastic kidneys.
多囊肾病和囊性肾发育不良中已报道了多种细胞生物学异常。这些疾病的一个共同特点是肾细胞成熟失败，这些肾细胞表面上类似于胚胎组织。凋亡是正常小鼠肾发生的一个特征，在肾发生过程中凋亡与形态发生有关，而在bcl-2基因敲除小鼠发育的小的囊性肾脏中发生暴发性凋亡。因此，我们使用碘化丙啶染色、原位末端标记和电子显微镜检查了人类多囊肾病和发育不良性肾病产前和产后样本中凋亡的位置和程度。在发育不良的肾脏中，细胞死亡在发育不良肾小管周围的未分化细胞中很突出，偶尔也见于囊性上皮细胞。产前和产后凋亡发生率均显著高于同龄正常对照。在多囊肾中，远离囊肿的未扩张肾小管周围的间质、囊肿之间的未扩张肾小管以及囊性上皮细胞中普遍存在凋亡。与对照相比，产后凋亡水平显著升高。在多囊性cpk/cpk小鼠模型的肾脏疾病早期和晚期也观察到类似的细胞死亡增加。我们推测，这些肾脏中细胞存活的失调可能反映了组织成熟不完全，并可能导致多囊肾中功能性肾组织的渐进性破坏以及囊性发育不良性肾中报道的自发退化。
