Distler Jörg, Distler Oliver
Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
Rheum Dis Clin North Am. 2008 Feb;34(1):145-59; vii. doi: 10.1016/j.rdc.2007.12.003.
The molecular mechanisms leading to tissue fibrosis were only poorly understood in the past, and even today the cause or trigger of systemic sclerosis is still unknown. Remarkable breakthrough findings have been obtained regarding the identification of key molecules, key cellular mechanisms, and key intracellular signaling cascades, which mediate the perpetuation of fibrosis rather than trigger it. These findings have true translational implications, because modifiers of these key mediators and key mechanisms are often in clinical use in other disease indications, such as cancer. This article summarizes the clinical and preclinical evidence of examples of these novel antifibrotic treatment approaches in systemic sclerosis, including stem cell transplantation, modifiers of transforming growth factor-beta1 signaling, intravenous immunoglobulins, tyrosine kinase inhibitors, and histone deacetylase inhibitors.
过去，人们对导致组织纤维化的分子机制了解甚少，即便在今天，系统性硬化症的病因或触发因素仍然未知。在关键分子、关键细胞机制以及关键细胞内信号级联反应的识别方面已取得显著的突破性发现，这些因素介导纤维化的持续存在而非引发纤维化。这些发现具有真正的转化意义，因为这些关键介质和关键机制的调节剂在其他疾病适应症（如癌症）中经常用于临床。本文总结了系统性硬化症中这些新型抗纤维化治疗方法实例的临床和临床前证据，包括干细胞移植、转化生长因子-β1信号调节剂、静脉注射免疫球蛋白、酪氨酸激酶抑制剂和组蛋白去乙酰化酶抑制剂。
