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      Reactive Oxygen Species and NOX Enzymes Are Emerging as Key Players in Cutaneous Wound Repair

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          Abstract

          Our understanding of the role of oxygen in cell physiology has evolved from its long-recognized importance as an essential factor in oxidative metabolism to its recognition as an important player in cell signaling. With regard to the latter, oxygen is needed for the generation of reactive oxygen species (ROS), which regulate a number of different cellular functions including differentiation, proliferation, apoptosis, migration, and contraction. Data specifically concerning the role of ROS-dependent signaling in cutaneous wound repair are very limited, especially regarding wound contraction. In this review we provide an overview of the current literature on the role of molecular and reactive oxygen in the physiology of wound repair as well as in the pathophysiology and therapy of chronic wounds, especially under ischemic and hyperglycemic conditions.

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          Oxidative stress shortens telomeres.

          Thomas von Zglinicki (2002)
          Telomeres in most human cells shorten with each round of DNA replication, because they lack the enzyme telomerase. This is not, however, the only determinant of the rate of loss of telomeric DNA. Oxidative damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it. I suggest here that oxidative stress is an important modulator of telomere loss and that telomere-driven replicative senescence is primarily a stress response. This might have evolved to block the growth of cells that have been exposed to a high risk of mutation.
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            Wound healing--aiming for perfect skin regeneration.

            P. Martin (1997)
            The healing of an adult skin wound is a complex process requiring the collaborative efforts of many different tissues and cell lineages. The behavior of each of the contributing cell types during the phases of proliferation, migration, matrix synthesis, and contraction, as well as the growth factor and matrix signals present at a wound site, are now roughly understood. Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.
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              The free radical theory of aging matures.

              K Beckman, B N AMES (1998)
              The free radical theory of aging, conceived in 1956, has turned 40 and is rapidly attracting the interest of the mainstream of biological research. From its origins in radiation biology, through a decade or so of dormancy and two decades of steady phenomenological research, it has attracted an increasing number of scientists from an expanding circle of fields. During the past decade, several lines of evidence have convinced a number of scientists that oxidants play an important role in aging. (For the sake of simplicity, we use the term oxidant to refer to all "reactive oxygen species," including O2-., H2O2, and .OH, even though the former often acts as a reductant and produces oxidants indirectly.) The pace and scope of research in the last few years have been particularly impressive and diverse. The only disadvantage of the current intellectual ferment is the difficulty in digesting the literature. Therefore, we have systematically reviewed the status of the free radical theory, by categorizing the literature in terms of the various types of experiments that have been performed. These include phenomenological measurements of age-associated oxidative stress, interspecies comparisons, dietary restriction, the manipulation of metabolic activity and oxygen tension, treatment with dietary and pharmacological antioxidants, in vitro senescence, classical and population genetics, molecular genetics, transgenic organisms, the study of human diseases of aging, epidemiological studies, and the ongoing elucidation of the role of active oxygen in biology.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 15 October 2017
                Publication date Collection: October 2017
                Volume: 18
                Issue: 10
                Electronic Location Identifier: 2149
                Affiliations
                [1 ]Department of Plastic, Reconstructive & Aesthetic Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland; ali.modarressi@ 123456hcuge.ch (A.M.); brigitte.pittet-cuenod@ 123456hcuge.ch (B.P.-C.)
                [2 ]Department of Human Genetics and Development, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland; michael.pepper@ 123456up.ac.za
                [3 ]SAMRC Extramural Unit for Stem Cell Research and Therapy, and Institute for Cellular and Molecular Medicine, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0002, South Africa
                Author notes
                [* ]Correspondence: dominik@ 123456levigne.eu ; Tel.: +41-798-626-777
                Author information
                https://orcid.org/0000-0002-0396-7511
                https://orcid.org/0000-0001-6406-2380
                Article
                Publisher ID: ijms-18-02149
                DOI: 10.3390/ijms18102149
                PMC ID: 5666831
                PubMed ID: 29036938
                SO-VID: 96df211c-ca75-4d5a-8af1-448e56528a9a
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 22 September 2017
                Date accepted : 10 October 2017
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: reactive oxygen species,nadph oxidase,nox enzymes,wound repair,wound healing,chronic wounds,wound contraction,re-epithelialization,hyperbaric oxygen therapy,oxidative stress
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: reactive oxygen species, nadph oxidase, nox enzymes, wound repair, wound healing, chronic wounds, wound contraction, re-epithelialization, hyperbaric oxygen therapy, oxidative stress

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