Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease
Joint Authors
Berger, Peter
Sampson, Natalie
Zenzmaier, Christoph
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-02-20
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Degenerative fibrotic diseases encompass numerous systemic and organ-specific disorders.
Despite their associated significant morbidity and mortality, there is currently no effective antifibrotic treatment.
Fibrosis is characterized by the development and persistence of myofibroblasts, whose unregulated deposition of extracellular matrix components disrupts signaling cascades and normal tissue architecture leading to organ failure and death.
The profibrotic cytokine transforming growth factor beta (TGFβ) is considered the foremost inducer of fibrosis, driving myofibroblast differentiation in diverse tissues.
This review summarizes recent in vitro and in vivo data demonstrating that TGFβ-induced myofibroblast differentiation is driven by a prooxidant shift in redox homeostasis.
Elevated NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H2O2) supported by concomitant decreases in nitric oxide (NO) signaling and reactive oxygen species scavengers are central factors in the molecular pathogenesis of fibrosis in numerous tissues and organs.
Moreover, complex interplay between NOX4-derived H2O2 and NO signaling regulates myofibroblast differentiation.
Restoring redox homeostasis via antioxidants or NOX4 inactivation as well as by enhancing NO signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases can inhibit and reverse myofibroblast differentiation.
Thus, dysregulated redox signaling represents a potential therapeutic target for the treatment of wide variety of different degenerative fibrotic disorders.
American Psychological Association (APA)
Sampson, Natalie& Berger, Peter& Zenzmaier, Christoph. 2014. Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease. BioMed Research International،Vol. 2014, no. 2014, pp.1-14.
https://search.emarefa.net/detail/BIM-448194
Modern Language Association (MLA)
Sampson, Natalie…[et al.]. Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease. BioMed Research International No. 2014 (2014), pp.1-14.
https://search.emarefa.net/detail/BIM-448194
American Medical Association (AMA)
Sampson, Natalie& Berger, Peter& Zenzmaier, Christoph. Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-14.
https://search.emarefa.net/detail/BIM-448194
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-448194