Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis.
Transforming growth factor beta (TGF-β) is the most potent pro-fibrogenic cytokine and its expression is increased in almost all of fibrotic diseases. Although signaling through Smad pathway is believed to play a central role in TGF-β's fibrogenesis, emerging evidence indicates that reactive oxygen species (ROS) modulate TGF-β's signaling through different pathways including Smad pathway. TGF-β1 increases ROS production and suppresses antioxidant enzymes, leading to a redox imbalance. ROS, in turn, induce/activate TGF-β1 and mediate many of TGF-β's fibrogenic effects, forming a vicious cycle (see graphic flow chart on the right). Here, we review the current knowledge on the feed-forward mechanisms between TGF-β1 and ROS in the development of fibrosis. Therapeutics targeting TGF-β-induced and ROS-dependent cellular signaling represents a novel approach in the treatment of fibrotic disorders.
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmi ngham, Birmingham, AL, USA. Electronic address: rliu@uab.edu.
Rui-Ming
RM
Liu
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmi ngham, Birmingham, AL, USA.
Leena P
LP
Desai
D000818:Animals; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D019255:NADPH Oxidases
Fibrosis; NADPH oxidases; Oxidative stress; PAI-1; TGF-β