Schnaper H William, Jandeska Sara, Runyan Constance E, Hubchak Susan C, Basu Rajit K, Curley Jessica F, Smith Ronald D, Hayashida Tomoko
Division of Kidney Diseases, Department of Pediatrics, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave.; Chicago, IL 60611-3008, USA.
Front Biosci (Landmark Ed). 2009 Jan 1;14(7):2448-65. doi: 10.2741/3389.
Transforming growth factor (TGF)-beta is a central stimulus of the events leading to chronic progressive kidney disease, having been implicated in the regulation of cell proliferation, hypertrophy, apoptosis and fibrogenesis. The fact that it mediates these varied events suggests that multiple mechanisms play a role in determining the outcome of TGF-beta signaling. Regulation begins with the availability and activation of TGF-beta and continues through receptor expression and localization, control of the TGF-beta family-specific Smad signaling proteins, and interaction of the Smads with multiple signaling pathways extending into the nucleus. Studies of these mechanisms in kidney cells and in whole-animal experimental models, reviewed here, are beginning to provide insight into the role of TGF-beta in the pathogenesis of renal dysfunction and its potential treatment.
转化生长因子(TGF)-β是导致慢性进行性肾病相关事件的核心刺激因素,参与细胞增殖、肥大、凋亡和纤维化形成的调控。它介导这些不同事件这一事实表明,多种机制在决定TGF-β信号转导结果中发挥作用。调控始于TGF-β的可用性和激活,并持续涉及受体表达和定位、TGF-β家族特异性Smad信号蛋白的控制,以及Smads与延伸至细胞核的多种信号通路的相互作用。本文综述了在肾细胞和全动物实验模型中对这些机制的研究,这些研究开始为TGF-β在肾功能障碍发病机制中的作用及其潜在治疗提供见解。