NADPH oxidase-dependent redox signaling in TGF-β-mediated fibrotic responses.
Uncontrolled fibrosis in organs like heart, kidney, liver and lung is detrimental and may lead to end-stage organ failure. Currently there is no effective treatment for fibrotic disorders. Transforming growth factor (TGF)-β has a fundamental role in orchestrating the process of fibrogenesis; however, interventions directly targeting TGF-β would have undesired systemic side effects due to the multiple physiological functions of TGF-β. Further characterization of the downstream signaling pathway(s) involved in TGF-β-mediated fibrosis may lead to discovery of novel treatment strategies for fibrotic disorders. Accumulating evidence suggests that Nox4 NADPH oxidase may be an important downstream effector in mediating TGF-β-induced fibrosis, while NADPH oxidase-dependent redox signaling may in turn regulate TGF-β/Smad signaling in a feed-forward manner. It is proposed that pharmacological inhibition of the Nox4 function may represent a novel approach in treatment of fibrotic disorders.
Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Fan
F
Jiang
Centre for Eye Research Australia, University of Melbourne, VIC 3002, Australia ; Department of Ophthalmology, University of Melbourne, VIC 3002, Australia.
Guei-Sheung
GS
Liu
Centre for Eye Research Australia, University of Melbourne, VIC 3002, Australia ; Department of Ophthalmology, University of Melbourne, VIC 3002, Australia.
Gregory J
GJ
Dusting
Centre for Eye Research Australia, University of Melbourne, VIC 3002, Australia.
Elsa C
EC
Chan
D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D002921:Cicatrix / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C422943:Nox4 protein, mouse
Fibrosis; NADPH oxidase; Nox4; Redox signaling; Transforming growth factor-β