Role of angiotensin and bcl-2 on renal organogenesis.

用新近建立的血管紧张素原和bcl2基因缺失的小鼠，研究了血管紧张素和bcl2在肾脏器官发生中的作用1)血管紧张素缺陷小鼠的胚胎肾脏表现出活跃的肾脏生成，在ATG+/-小鼠和ATG+/+小鼠中也观察到。此外，胚胎12岁时从ATG-/-胚胎获得的后肾显示出与外源血管紧张素II生长的ATG-/-胚胎的后肾相似的输尿管芽和小管的分枝形态发生，在新生的ATG-/-小鼠中，我们观察到统一的骨盆扩张伴随着粗糙的髓质。出生后4周，肾积水持续，肾乳头萎缩。此外，出生后短短两周就出现了血管壁的粗隆，这一现象令人印象深刻。原位杂交和免疫组织化学结果显示，随着VSMC的增生和肾素蛋白的募集，肾素mRNA的表达明显增强。总而言之，r…更多的内毒素-血管紧张素系统似乎不是体内肾脏形成的必要条件。此外，在无血管紧张素II和低血压的情况下，系膜中VSMC的增殖和平滑肌表型的表达也是可以诱导的。2)bcl2基因缺陷小鼠在异常的肾形成过程中发生了广泛的细胞凋亡。在bcl2-/-小鼠中，正常的胚胎第13天(E-13)检测到最初的肾单位的诱导。从E-13到E-16，BCL-2-/-小鼠肾单位数显著减少(1/5)，E-17-/-小鼠肾单位数显著减少(1/5)。形态计量学显示bcl2+/-小鼠与bcl2+/+小鼠形态无明显差异。凋亡细胞主要见于间充质，少见于肾小管。输尿管芽间几乎未见细胞凋亡。在BCL-2-/-小鼠中，E-17~E-19的小鼠输尿管分支不活跃，输尿管芽不充分卷曲，并伴有间质细胞的暴发性凋亡。新生的bcl2-/-小鼠缺乏生肾区，表现为肾脏发育不良。因此，在体内诱导肾单位的过程中，bcl2似乎抑制了肾干细胞的凋亡。较少

Role of angiotensin and bcl-2 on renal organogenesis was investigated using recently established angiotensinogen and bcl-2 gene desrupted mice.1)Angiotensin deficient mice.Embryonic kidneys in Atg -/- mice from E13 to E18 exhibited active nephrogenesis, as also observed in Atg +/- mice and Atg +/+ mice. Futhermore, metanephroi harvested at E12 from Atg -/- embryos showed similar branching morphogenesis of ureteric bud and tubulogenesis as metanephroi from Atg -/- embryos grown with exogenous angiotensin II.In newborn Atg -/- mice, we observed unifrom dilatation of the pelvis accompanied by a coarse medulla. Hydronephrosis continued and renal papillae underwent atrophy for the 4 weeks after birth. Moreover, hickening of vascular walls as little as two weeks after birth was impressive. in situ hybridization and immunohistochemistry demonctrated that expression of renin mRNA became prominent in parallel with hyperplasia of VSMC,as well as recruitment of renin protein. In conclusion, the r … More enin-angiotensin system appears not be essential for nephrogenesis in vivo. Furthermore, hyperplasia of VSMC and expression of the smoothmuscle phenotype in the mesangium are inducible even in the absence of angiotensin II,with hypotension, in vivo.2)bcl-2 deficient miceExtensive apoptosis occurred during abnormal nephrogenesis in bcl-2 deficient mice. In bcl-2 -/- mice, initial induction of nephron was detected by embryonic day 13 (E-13) as normal. Then, apoptotic cells became five times more frequent at E-13 to E-16 with a significant reduction (1/5) in nephron number at E-17 to E-19 in bcl-2 -/- mice compared to bcl-2 +/+ mice. No morphological difference was evident between bcl-2 +/- mice and bcl-2 +/+ mice by morphometry. Apoptotic cells were found mainly among the mesenchyme and less frequently in tubuli. Little apoptosis among ureteric buds was noted. In bcl-2 -/- mice at E-17 to E-19, inactive branching and insufficient convolution of ureteric buds were accompanied by fulminant apoptosis in the mesenchyme. Neonatal bcl-2 -/- mice lacked the nephrogenic zone, exhibiting renal hypoplasia. Thus, bcl-2 seems to inhibit apoptosis in renal stem cells during the induction of nephron in vivo. Less