Gressner Axel M, Weiskirchen Ralf, Breitkopf Katja, Dooley Steven
Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, D-52074 Aachen, Germany.
Front Biosci. 2002 Apr 1;7:d793-807. doi: 10.2741/A812.
TGF-beta has multiple profibrogenic but also anti-inflammatory and immunosuppressive effects. The balance of these actions is required for maintaining tissue homeostasis and an aberrant expression of TGF-beta is involved in a number of disease processes in the liver. In addition to its fibrogenic action leading to transdifferentiation of hepatic stellate cells into myofibroblasts, TGF-beta is also an important negative regulator of proliferation and an inducer of apoptosis. The major portion of TGF-beta is secreted as part of an inactive complex and the details of the activation process in liver have not yet been elucidated. The initially striking simplicity of the core TGF-beta/Smad signaling pathways is rapidly giving way to a much more complex view of intracellular signal transduction mechanisms and recent work has demonstrated the importance of cross-talk among different signaling pathways to either specify, enhance, or inhibit TGF-beta responses. The ubiquitous pathophysiologic relevance of TGF-beta suggests its measurement in blood as a diagnostic tool. Other strategies aim at inhibition of TGF-beta1 function or synthesis as a primary target for the development of antifibrotic strategies and recent advances in cell biology have opened several ways to approach the inhibition of TGF-beta action.
转化生长因子-β（TGF-β）具有多种促纤维化作用，但也具有抗炎和免疫抑制作用。维持组织稳态需要这些作用的平衡，而TGF-β的异常表达与肝脏的许多疾病过程有关。除了其导致肝星状细胞转分化为肌成纤维细胞的促纤维化作用外，TGF-β还是细胞增殖的重要负调节因子和细胞凋亡的诱导剂。TGF-β的大部分以无活性复合物的形式分泌，肝脏中激活过程的细节尚未阐明。最初核心TGF-β/Smad信号通路惊人的简单性正迅速让位于对细胞内信号转导机制更为复杂的认识，最近的研究表明不同信号通路之间的相互作用对于确定、增强或抑制TGF-β反应至关重要。TGF-β普遍的病理生理相关性表明可将其在血液中的检测作为一种诊断工具。其他策略旨在抑制TGF-β1的功能或合成，作为抗纤维化策略开发的主要靶点，细胞生物学的最新进展为抑制TGF-β作用开辟了多种途径。
