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空腔 (V) ATPase (V-ATPase) 在脏发育过程中调节尿路芽 (UB) 分支形态发生
Ihor V Yosipiv1, Hongbing Liu1, Nazih L Nakhoul2
1Section of Pediatric Nephrology, Department of Pediatrics, Tulane University Health Sciences Center, New Orleans, LA 70112.
概括
空腔H+-ATPase (V-ATPase) 活性对于脏尿道芽的分支至关重要. 抑制V-ATPase或诱导酸化通过影响细胞迁移和细胞内pH而减少分支.
科学领域:
- 发展生物学 发展生物学
- 细胞生理学 细胞生理学
- 脏生物学 脏生物学
背景情况:
- 尿道芽 (UB) 的分支对脏发育至关重要.
- 林受体 (PRR/ATP6AP2),是真空H+-ATPase (V-ATPase) 的一个子单元,对于正常的UB分支至关重要.
- 在UB分支中V-ATPase活性,酸性和细胞内pH (pHi) 的作用需要进一步研究.
研究的目的:
- 调查V-ATPase活性,酸性和UB细胞细胞内pH调节UB分支形态发生的假设.
- 确定V-ATPase抑制和酸化对UB分支和细胞迁移的影响.
主要方法:
- 使用时间缩短显微镜对E12.5小鼠脏进行活体培养.
- 对于UB细胞的体外穿孔迁移试验.
- 使用pH指标进行细胞内pH (pHi) 测量.
- 诱导超性和代谢性化症.
主要成果:
- 用巴菲洛米辛抑制V-ATPase在体外减少了UB细胞迁移.
- 巴菲洛米辛治疗,高酸性和代谢性酸性显著减少了培养中的UB分支.
- 酸性疾病导致UB尖端数量显著减少.
结论:
- 完整的V-ATPase活性对于脏发育期间正常的尿道芽分支是必不可少的.
- 在UB细胞细胞内pH值的V-ATPase依赖的减少可能会通过抑制细胞迁移来损害分支.
- 酸化通过破坏UB分支形态发生而对脏发育产生负面影响.
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