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      Wound healing and inflammation genes revealed by array analysis of 'macrophageless' PU.1 null mice

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      1 , 4 , 2 , 2 , 1 , 3 ,
      Genome Biology
      BioMed Central

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          Abstract

          To define the events in wound healing that are independent of inflammation, gene expression during wound healing was profiled in wild-type mice and PU.1 null mice, which cannot raise the standard inflammatory response but which can repair skin wounds rapidly.

          Abstract

          Background

          Wound healing is a complex process requiring the collaborative efforts of different tissues and cell lineages, and involving the coordinated interplay of several phases of proliferation, migration, matrix synthesis and contraction. Tissue damage also triggers a robust influx of inflammatory leukocytes to the wound site that play key roles in clearing the wound of invading microbes but also release signals that may be detrimental to repair and lead to fibrosis.

          Results

          To better define key cellular events pivotal for tissue repair yet independent of inflammation we have used a microarray approach to determine a portfolio of over 1,000 genes expressed across the repair response in a wild-type neonatal mouse versus its PU.1 null sib. The PU.1 null mouse is genetically incapable of raising the standard inflammatory response, because it lacks macrophages and functioning neutrophils, yet repairs skin wounds rapidly and with reduced fibrosis. Conversely, by subtraction, we have determined genes that are either expressed by leukocytes, or upregulated by fibroblasts, endothelial cells, muscle cells and others at the wound site, as a consequence of inflammation. To determine the spatial expression pattern for several genes in each cluster we have also performed in situ hybridization studies.

          Conclusions

          Cluster analysis of genes expressed after wounding wild-type mice versus PU.1 null sibs distinguishes between tissue repair genes and genes associated with inflammation and its consequences. Our data reveal and classify several pools of genes, giving insight into their likely functions during repair and hinting at potential therapeutic targets.

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          Most cited references48

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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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            Regulation of wound healing by growth factors and cytokines.

            Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process.
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              • Record: found
              • Abstract: not found
              • Article: not found

              Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival.

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                Author and article information

                Journal
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1465-6906
                1465-6914
                2005
                23 December 2004
                : 6
                : 1
                : R5
                Affiliations
                [1 ]Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, UK
                [2 ]Pfizer Global Research and Development, Sandwich, Kent, CT13 9NJ, UK
                [3 ]Departments of Physiology and Biochemistry, University of Bristol, Bristol, BS8 1TD, UK
                [4 ]Current Address: Molecular Neuroscience Group, School of Medicine, University of Birmingham, Birmingham, B15 2TH, UK
                Article
                gb-2004-6-1-r5
                10.1186/gb-2004-6-1-r5
                549066
                15642097
                f4d4bc9f-3529-459f-99f1-5d013d270d23
                Copyright © 2004 Cooper et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 September 2004
                : 29 October 2004
                : 24 November 2004
                Categories
                Research

                Genetics
                Genetics

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