小RabGTPases,最大的一组小单体GTPases,调节细胞中的囊泡运输,它们是许多细胞过程不可或缺的。它们在神经系统疾病中的作用,如癌症和炎症已被广泛研究,但是它们对肾脏疾病的影响尚未得到深入研究。已证明Rab3a及其效应物Rabphillin-3A(Rph3A)表达存在于小鼠大鼠和人类正常肾脏的足细胞中,围绕着包含在足突中的囊泡,它们在有蛋白尿的疾病中过度表达。此外,Rab3A敲除小鼠模型在高糖喂养动物的足细胞中诱导了深刻的细胞骨架变化。同样,果蝇模型中的RphA干扰在肾细胞中产生结构和功能损伤,同时过滤能力和肾细胞数量减少。在相同的RphA干扰模型中,心脏纤维结构的变化,打开一个问题,如果Rab3A功能障碍会同时在心脏和肾脏细胞中产生损害,一个有吸引力的领域,将来需要关注。
Small Rab GTPases, the largest group of small monomeric GTPases, regulate vesicle trafficking in cells, which are integral to many cellular processes. Their role in neurological diseases, such as cancer and inflammation have been extensively studied, but their implication in kidney disease has not been researched in depth.
Rab3a and its effector Rabphillin-3A (Rph3A) expression have been demonstrated to be present in the podocytes of normal kidneys of mice rats and humans, around vesicles contained in the foot processes, and they are overexpressed in diseases with proteinuria. In addition, the
Rab3A knockout mice model induced profound cytoskeletal changes in podocytes of high glucose fed animals. Likewise, RphA interference in the Drosophila model produced structural and functional damage in nephrocytes with reduction in filtration capacities and nephrocyte number. Changes in the structure of cardiac fiber in the same RphA-interference model, open the question if
Rab3A dysfunction would produce simultaneous damage in the heart and kidney cells, an attractive field that will require attention in the future.