Reiser Jochen, Sever Sanja, Faul Christian
Department of Medicine, Rush University Medical Center, 1735 West Harrison Street, Cohn Building, Suite 724, Chicago, IL 60612, USA.
Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Nat Rev Nephrol. 2014 Feb;10(2):104-15. doi: 10.1038/nrneph.2013.274. Epub 2014 Jan 7.
The mammalian kidney filtration barrier is a complex multicellular, multicomponent structure that maintains homeostasis by regulating electrolytes, acid-base balance, and blood pressure (via maintenance of salt and water balance). To perform these multiple functions, podocytes--an important component of the filtration apparatus--must process a series of intercellular signals. Integrating these signals with diverse cellular responses enables a coordinated response to various conditions. Although mature podocytes are terminally differentiated and cannot proliferate, they are able to respond to growth factors. It is possible that the initial response of podocytes to growth factors is beneficial and protective, and might include the induction of hypertrophic cell growth. However, extended and/or uncontrolled growth factor signalling might be maladaptive and could result in the induction of apoptosis and podocyte loss. Growth factors signal via the activation of receptor tyrosine kinases (RTKs) on their target cells and around a quarter of the 58 RTK family members that are encoded in the human genome have been identified in podocytes. Pharmacological inhibitors of many RTKs exist and are currently used in experimental and clinical cancer therapy. The identification of pathological RTK-mediated signal transduction pathways in podocytes could provide a starting point for the development of novel therapies for glomerular disorders.
哺乳动物的肾脏滤过屏障是一种复杂的多细胞、多组分结构，通过调节电解质、酸碱平衡和血压（通过维持盐和水平衡）来维持体内稳态。为了执行这些多种功能，足细胞（滤过装置的重要组成部分）必须处理一系列细胞间信号。将这些信号与不同的细胞反应整合起来，能够对各种情况做出协调反应。虽然成熟的足细胞是终末分化的，不能增殖，但它们能够对生长因子做出反应。足细胞对生长因子的初始反应可能是有益和保护性的，可能包括诱导肥大细胞生长。然而，延长和/或不受控制的生长因子信号传导可能是适应不良的，并可能导致细胞凋亡和足细胞丢失。生长因子通过其靶细胞上受体酪氨酸激酶（RTK）的激活来发出信号，在人类基因组中编码的58个RTK家族成员中，约四分之一已在足细胞中被鉴定出来。许多RTK的药理抑制剂已经存在，目前用于实验性和临床癌症治疗。鉴定足细胞中病理性RTK介导的信号转导途径可为开发肾小球疾病的新疗法提供一个起点。
