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细胞内囊泡运输中的小 Rab GTPases:以肾脏中的 Rab3A/Raphillin-3A 复合物为例。

Small Rab GTPases in Intracellular Vesicle Trafficking: The Case of Rab3A/Raphillin-3A Complex in the Kidney.

机构信息

Cardiometabolic and Renal Risk Research Group, INCLIVA Biomedical Research Institute, 46010 Valencia, Spain.

Physiopathology of Cellular and Organic Oxidative Stress Group, University of Valencia, 46100 Valencia, Spain.

出版信息

Int J Mol Sci. 2021 Jul 18;22(14):7679. doi: 10.3390/ijms22147679.

Abstract

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, interference in the 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 -interference model, open the question if dysfunction would produce simultaneous damage in the heart and kidney cells, an attractive field that will require attention in the future.

摘要

小分子 GTP 酶,是最大的小分子单体 GTP 酶家族,调节细胞内囊泡运输,这对许多细胞过程至关重要。它们在神经疾病(如癌症和炎症)中的作用已经得到了广泛研究,但它们在肾脏疾病中的作用尚未深入研究。Rab3a 和其效应因子 Rabphillin-3A(Rph3A)的表达已被证明存在于正常小鼠、大鼠和人类肾脏的足突中的囊泡周围,并且在蛋白尿疾病中过度表达。此外,高糖喂养的 Rab3A 敲除小鼠模型诱导足突细胞中的细胞骨架发生深刻变化。同样,在该模型中进行干扰会导致肾细胞的结构和功能损伤,滤过能力和肾细胞数量减少。同一干扰模型中心脏纤维结构的变化提出了一个问题,如果 功能障碍是否会同时导致心脏和肾脏细胞的损伤,这是一个有吸引力的领域,未来需要关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bb8/8303874/c462a0836a10/ijms-22-07679-g001.jpg

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