Redox-fibrosis: Impact of TGFβ1 on ROS generators, mediators and functional consequences.
Fibrosis is one of the most prevalent features of age-related diseases like obesity, diabetes, non-alcoholic fatty liver disease, chronic kidney disease, or cardiomyopathy and affects millions of people in all countries. Although the understanding about the pathophysiology of fibrosis has improved a lot during the recent years, a number of mechanisms still remain unknown. Although TGF-β1 signaling, loss of metabolic homeostasis and chronic low-grade inflammation appear to play important roles in the pathogenesis of fibrosis, recent evidence indicates that oxidative stress and the antioxidant system may also be crucial for fibrosis development and persistence. These findings point to a concept of a redox-fibrosis where the cellular oxidant and antioxidant system could be potential therapeutic targets. The current review aims to summarize the existing links between TGF-β1 signaling, generation and action of reactive oxygen species, expression of antioxidative enzymes, and functional consequences including epigenetic redox-mediated responses during fibrosis.
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Kati
K
Richter
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Anja
A
Konzack
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland; Center of Excellence in Cell-Extracellular Matrix Research, Finland.
Taina
T
Pihlajaniemi
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland; Center of Excellence in Cell-Extracellular Matrix Research, Finland.
Ritva
R
Heljasvaara
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland. Electronic address: tkietzm@gwdg.de.
Thomas
T
Kietzmann
D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000975:Antioxidants / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
Antioxidants; Antioxidative enzymes; Diet; Fibrosis; Matrix; ROS