Biochimica et Biophysica Acta (BBA) - General Subjects
Invited reviewRedox signals in wound healing
Section snippets
Hemostasis
As the first step in response to injury, blood flow around the injured site increases helping to bring in blood-borne products such as the white blood cells, antibacterial proteins and other relevant products as first-aid. ROS and the redox state are important in the control of blood coagulation and thrombosis [24]. Furthermore, vascular injury triggers endothelial exocytosis of granules, releasing pro-inflammatory and pro-thrombotic mediators into the blood by redox-sensitive mechanisms [25].
Inflammation
H2O2 has a fine-tuning regulatory role, comprising both a pro-inflammatory control loop that increases pathogen removal and an anti-inflammatory control loop, which avoids an exacerbated harmful inflammatory response [45]. Phagocytes contribute to innate immunity by mounting a respiratory burst that helps kill internalized bacteria. Neutrophils infiltrating to the wound site cleanse the wound of foreign particles and bacteria and are then extruded with the eschar or phagocytosed by macrophages.
Re-epithelialization
Wound closure of epithelial tissues must occur efficiently to restore rapidly their barrier function. Adult epidermal keratinocytes migrate by crawling, a process that requires protrusion of the plasma membrane at the front of the cell and contraction of the cell body at the rear. Insulin-like growth factor 1 (IGF-1) stimulates membrane protrusion and facilitates cell spreading via activation of Rho family proteins [65]. IGF structure and function is subject to tight redox control [66], [67].
Vascularization
Vascularization, under physiological or pathophysiological conditions, typically takes place by one or more of the following processes: angiogenesis, vasculogenesis, arteriogenesis and lymphangiogenesis. Angiogenesis refers to the process by which new blood vessels develop from pre-existing blood vessels by sprouting or intussusception. De novo formation of new blood vessels from primitive cells during say early embryonic development takes place by vasculogenesis. As it is now known that under
Nitric oxide in wound healing
In the late 1970s, research was unfolding that implicated nitric oxide involvement in the process of vasodilation. By 1986, research culminated in the identification of nitric oxide as the endothelium-derived relaxing factor responsible for the maintenance of vascular tone, thus implicating nitric oxide as a potential wound-healing agent. Numerous aspects of redox biology are sensitive to nitric oxide (NO), a nitrogen-centered free radical gas. For example, both superoxide and nitric oxide are
Conclusion
In sum, numerous aspects of wound healing are subject to redox control. Thus, development of a thorough understanding of how endogenous ROS generated in wound-related cells may influence the healing process becomes critically important. Such an understanding could result in novel redox-based strategies to treat wounds. Current results with growth factor therapy of wounds do not meet expectations. Many of these growth factors, like PDGF, rely on ROS for functioning. Thus, redox-based strategies
Acknowledgment
Supported by NIH RO1 grants GM069589 and GMl077185 to CKS.
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