NADPH oxidase enzymes in skin fibrosis: Molecular targets and therapeutic agents

Olubukola Babalola, Andrew Mamalis, Hadar Lev-Tov, Jared Jagdeo

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

Fibrosis is characterized by the excessive deposition of extracellular matrix components eventually resulting in organ dysfunction and failure. In dermatology, fibrosis is the hallmark component of many skin diseases, including systemic sclerosis, graft-versus-host disease, hypertrophic scars, keloids, nephrogenic systemic fibrosis, porphyria cutanea tarda, restrictive dermopathy and other conditions. Fibrotic skin disorders may be debilitating and impair quality of life. There are few FDA-approved anti-fibrotic drugs; thus, research in this area is crucial in addressing this deficiency. Recent investigations elucidating the pathogenesis of skin fibrosis have implicated endogenous reactive oxygen species produced by the multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzyme complex. In this review, we discuss Nox enzymes and their role in skin fibrosis. An overview of the Nox enzyme family is presented and their role in the pathogenesis of skin fibrosis is discussed. The mechanisms by which Nox enzymes influence specific fibrotic skin disorders are also reviewed. Finally, we describe the therapeutic approaches to ameliorate skin fibrosis by directly targeting Nox enzymes with the use of statins, p47phox subunit modulators, or GKT137831, a competitive inhibitor of Nox enzymes. Nox enzymes can also be targeted indirectly via scavenging ROS with antioxidants. We believe that Nox modulators are worthy of further investigation and have the potential to transform the management of skin fibrosis by dermatologists.

Original languageEnglish (US)
Pages (from-to)313-330
Number of pages18
JournalArchives of Dermatological Research
Volume306
Issue number4
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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NADPH Oxidase
NADP
Oxidoreductases
Fibrosis
Skin
Enzymes
Therapeutics
Nephrogenic Fibrosing Dermopathy
Porphyria Cutanea Tarda
Hypertrophic Cicatrix
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Keloid
Systemic Scleroderma
Graft vs Host Disease
Dermatology
Skin Diseases
Extracellular Matrix
Reactive Oxygen Species
Antioxidants
Quality of Life

Keywords

  • NADPH oxidase
  • Nox
  • Reactive oxygen species
  • ROS
  • Skin fibrosis
  • Transforming growth factor-beta

ASJC Scopus subject areas

  • Dermatology

Cite this

NADPH oxidase enzymes in skin fibrosis : Molecular targets and therapeutic agents. / Babalola, Olubukola; Mamalis, Andrew; Lev-Tov, Hadar; Jagdeo, Jared.

In: Archives of Dermatological Research, Vol. 306, No. 4, 01.01.2014, p. 313-330.

Research output: Contribution to journalReview article

Babalola, Olubukola ; Mamalis, Andrew ; Lev-Tov, Hadar ; Jagdeo, Jared. / NADPH oxidase enzymes in skin fibrosis : Molecular targets and therapeutic agents. In: Archives of Dermatological Research. 2014 ; Vol. 306, No. 4. pp. 313-330.
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