Abstract
The Transforming Growth Factor-beta (TGF-β) pathway plays essential roles in liver development and homeostasis and become a relevant factor involved in different liver pathologies, particularly fibrosis and cancer. The family of NADPH oxidases (NOXs) has emerged in recent years as targets of the TGF-β pathway mediating many of its effects on hepatocytes, stellate cells and macrophages. This review focuses on how the axis TGF-β/NOXs may regulate the biology of different liver cells and how this influences physiological situations, such as liver regeneration, and pathological circumstances, such as liver fibrosis and cancer. Finally, we discuss whether NOX inhibitors may be considered as potential therapeutic tools in liver diseases.
Highlights
The Transforming Growth Factor-beta (TGF-β) family of polypeptides plays important roles in the regulation of embryogenesis and adult tissue homeostasis, and it is implicated in pathophysiological mechanisms that are the basis of several diseases, including fibrosis and cancer [1,2]
Considering that NOX1, NOX2, and NOX4 have been widely studied in liver physiology and pathology, in this review we will focus on these three members of the family
An additional study has demonstrated that higher NOX4 mRNA expression levels in hepatocellular carcinoma (HCC) patients are significantly associated with prolonged overall survival, whereas increased NOX1/NOX2 expression is significantly correlated with a poor overall survival, indicating that while NOX4 behaves as a tumor suppressor in HCC, NOX1 and NOX2 may act as tumor promoters [155]
Summary
The Transforming Growth Factor-beta (TGF-β) family of polypeptides plays important roles in the regulation of embryogenesis and adult tissue homeostasis, and it is implicated in pathophysiological mechanisms that are the basis of several diseases, including fibrosis and cancer [1,2]. The nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase (NOX) family produces reactive oxygen species (ROS) that play relevant roles in signal transduction pathways [3]. 2. NADPH Oxidase Family Members In most mammals, seven isoforms of NOX have been described: NOX1–5 and two dual oxidases (DUOX1–2). NADPH Oxidase Family Members In most mammals, seven isoforms of NOX have been described: NOX1–5 and two dual oxidases (DUOX1–2) They use NADPH as an electron donor to reduce oxygen to superoxide anion (O2−), which is converted to hydrogen peroxide (H2O2) either spontaneously or by enzymatic action. The expression of other mammalian NOX homologues has been found in various cell types and tissues, playing roles in maintaining their normal physiology and activity. Dysregulation in NOX expression or activation leads to several pathological consequences, such as cardiovascular diseases, cancer, diabetes, and neurodegenerative diseases [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
