Department of Environmental Health Sciences, School of Public Health, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Free Radic Biol Med. 2010 Jan 1;48(1):1-15. doi: 10.1016/j.freeradbiomed.2009.09.026. Epub 2009 Oct 2.
Transforming growth factor beta (TGF-beta) is the most potent and ubiquitous profibrogenic cytokine, and its expression is increased in almost all the fibrotic diseases and in experimental fibrosis models. TGF-beta increases reactive oxygen species production and decreases the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, which mediates many of the fibrogenic effects of TGF-beta in various types of cells. A decreased GSH concentration is also observed in human fibrotic diseases and in experimental fibrosis models. Although the biological significance of GSH depletion in the development of fibrosis remains obscure, GSH and N-acetylcysteine, a precursor of GSH, have been used in clinics for the treatment of fibrotic diseases. This review summarizes recent findings in the field to address the potential mechanism whereby oxidative stress mediates fibrogenesis induced by TGF-beta and the potential therapeutic value of antioxidant treatment in fibrotic diseases.
转化生长因子-β(TGF-β)是最有效和最普遍的促纤维化细胞因子,几乎所有的纤维化疾病和实验性纤维化模型中其表达均增加。TGF-β增加活性氧的产生并降低谷胱甘肽(GSH)的浓度,GSH 是细胞内最丰富的游离巯基和一种重要的抗氧化剂,介导 TGF-β在各种类型细胞中的许多促纤维化作用。在人类纤维化疾病和实验性纤维化模型中也观察到 GSH 浓度降低。虽然 GSH 耗竭在纤维化发展中的生物学意义尚不清楚,但 GSH 和 N-乙酰半胱氨酸(GSH 的前体)已在临床上用于治疗纤维化疾病。这篇综述总结了该领域的最新发现,以探讨氧化应激介导 TGF-β诱导的纤维化的潜在机制,以及抗氧化治疗在纤维化疾病中的潜在治疗价值。