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      Redox Signaling in Diabetic Wound Healing Regulates Extracellular Matrix Deposition

      1 , 2 , 1 , 2 , 3
      Antioxidants & Redox Signaling
      Mary Ann Liebert Inc

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          Abstract

          <p id="d7139128e215"> <b> <i>Significance:</i> </b> Impaired wound healing is a major complication of diabetes, and can lead to development of chronic foot ulcers in a significant number of patients. Despite the danger posed by poor healing, very few specific therapies exist, leaving patients at risk of hospitalization, amputation, and further decline in overall health. </p><p id="d7139128e223"> <b> <i>Recent Advances:</i> </b> Redox signaling is a key regulator of wound healing, especially through its influence on the extracellular matrix (ECM). Normal redox signaling is disrupted in diabetes leading to several pathological mechanisms that alter the balance between reactive oxygen species (ROS) generation and scavenging. Importantly, pathological oxidative stress can alter ECM structure and function. </p><p id="d7139128e231"> <b> <i>Critical Issues:</i> </b> There is limited understanding of the specific role of altered redox signaling in the diabetic wound, although there is evidence that ROS are involved in the underlying pathology. </p><p id="d7139128e239"> <b> <i>Future Directions:</i> </b> Preclinical studies of antioxidant-based therapies for diabetic wound healing have yielded promising results. Redox-based therapeutics constitute a novel approach for the treatment of wounds in diabetes patients that deserve further investigation. <i>Antioxid. Redox Signal</i>. 27, 823–838. </p>

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          Most cited references150

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          Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process.

          Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.
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            Oxidative stress in normal and impaired wound repair.

            A large percentage of the population suffers from wound healing abnormalities, in particular aged individuals, patients with diabetes, and those treated with immunosuppressive drugs, chemo- or radiotherapy. The mechanisms underlying the impaired healing response are still poorly understood. Recent studies provided strong evidence for a role of oxidative stress in the pathogenesis of non-healing ulcers. Therefore, it is of major importance to identify and functionally characterize the factors involved in the generation and detoxification of reactive oxygen species (ROS). This will provide the basis for the development of new strategies for therapeutic intervention. In this review we summarize the current information about the roles of low molecular weight antioxidants and ROS-detoxifying enzymes in normal and impaired wound repair, and we report on the consequences of their modulation at the wound site.
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              Oxygen in acute and chronic wound healing.

              Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defence, angiogenesis and collagen synthesis. Even though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. This article provides an overview on the role of oxygen in wound healing and chronic wound pathogenesis, a brief insight into systemic and topical oxygen treatment, and a discussion of the role of wound tissue oximetry. Thus, the aim is to improve the understanding of the role of oxygen in wound healing and to advance our management of wound patients.
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                Author and article information

                Journal
                Antioxidants & Redox Signaling
                Antioxidants & Redox Signaling
                Mary Ann Liebert Inc
                1523-0864
                1557-7716
                October 20 2017
                October 20 2017
                : 27
                : 12
                : 823-838
                Affiliations
                [1 ]Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
                [2 ]Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, Connecticut.
                [3 ]Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
                Article
                10.1089/ars.2017.7263
                5647483
                28699352
                bd9f66a8-4b87-4b54-944e-60f03ec52fad
                © 2017

                http://www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/

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