MAPKAPK-2 Signaling Is Critical for Cutaneous Wound Healing

Thuraisingam, Thusanth; Xu, Yong; Eadie, Kalyn; Heravi, Mitra; Guiot, Marie-Cristine; Greemberg, Rony; Gaestel, Matthias; Radzioch, Danuta

doi:10.1038/jid.2009.209

Cited by 44 publications

(28 citation statements)

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“…Additional studies indicate that p38␣ is the predominant isoform involved in cytokine production in vivo following lipopolysaccharide (LPS) stimulation (43), and gene transfer of p38␣ and the upstream activator MKK3 significantly increased expression of bFGF and PDGF-A in the normal heart (45), further supporting the concept of independent, non-redundant functions of p38 MAPK isoforms. In addition to p38␣, knockdown of the p38 MAPK pathway protein MK2 or HSP27 in stromal cells also reduced cord formation along with VEGF, bFGF, and IL-6 secretion, a result substantiated in MK2 knockout mice, where reduced angiogenesis in wound healing is in concert with reduced expression of several cytokines (GM-CSF, VEGF, IFN␥, MCP1, TNF, IL-6, and IL-1␤) compared with wild-type mice (46). In addition, targeted deletion of MK2 in macrophages led to decreased production of LPS-induced tumor necrosis factor (TNF), IL-6, and other cytokines (47).…”

Section: Discussionmentioning

confidence: 76%

LY2228820 Dimesylate, a Selective Inhibitor of p38 Mitogen-activated Protein Kinase, Reduces Angiogenic Endothelial Cord Formation in Vitro and in Vivo

Tate

Blosser

Wyss³

et al. 2013

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 76%

LY2228820 Dimesylate, a Selective Inhibitor of p38 Mitogen-activated Protein Kinase, Reduces Angiogenic Endothelial Cord Formation in Vitro and in Vivo

Tate

Blosser

Wyss³

et al. 2013

Journal of Biological Chemistry

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“…MK2 activation is also required for cytokine production during inflammatory responses [129]. It was recently demonstrated that MK2 activity is essential to cutaneous wound healing [130] and thus an enzyme of this group may be a modulator of tissue injury/immune response in AM epithelia.…”

Section: Resultsmentioning

confidence: 99%

An Insight into the Transcriptome of the Digestive Tract of the Bloodsucking Bug, Rhodnius prolixus

et al. 2014

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The bloodsucking hemipteran Rhodnius prolixus is a vector of Chagas' disease, which affects 7–8 million people today in Latin America. In contrast to other hematophagous insects, the triatomine gut is compartmentalized into three segments that perform different functions during blood digestion. Here we report analysis of transcriptomes for each of the segments using pyrosequencing technology. Comparison of transcript frequency in digestive libraries with a whole-body library was used to evaluate expression levels. All classes of digestive enzymes were highly expressed, with a predominance of cysteine and aspartic proteinases, the latter showing a significant expansion through gene duplication. Although no protein digestion is known to occur in the anterior midgut (AM), protease transcripts were found, suggesting secretion as pro-enzymes, being possibly activated in the posterior midgut (PM). As expected, genes related to cytoskeleton, protein synthesis apparatus, protein traffic, and secretion were abundantly transcribed. Despite the absence of a chitinous peritrophic membrane in hemipterans - which have instead a lipidic perimicrovillar membrane lining over midgut epithelia - several gut-specific peritrophin transcripts were found, suggesting that these proteins perform functions other than being a structural component of the peritrophic membrane. Among immunity-related transcripts, while lysozymes and lectins were the most highly expressed, several genes belonging to the Toll pathway - found at low levels in the gut of most insects - were identified, contrasting with a low abundance of transcripts from IMD and STAT pathways. Analysis of transcripts related to lipid metabolism indicates that lipids play multiple roles, being a major energy source, a substrate for perimicrovillar membrane formation, and a source for hydrocarbons possibly to produce the wax layer of the hindgut. Transcripts related to amino acid metabolism showed an unanticipated priority for degradation of tyrosine, phenylalanine, and tryptophan. Analysis of transcripts related to signaling pathways suggested a role for MAP kinases, GTPases, and LKBP1/AMP kinases related to control of cell shape and polarity, possibly in connection with regulation of cell survival, response of pathogens and nutrients. Together, our findings present a new view of the triatomine digestive apparatus and will help us understand trypanosome interaction and allow insights into hemipteran metabolic adaptations to a blood-based diet.

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“…Prevention of recruitment and activation of natural killer T cell (NKT) to the wound bed leads to enhanced wound healing [66]. Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2 or MK2) gene expression in macrophages is critical in wound healing based upon studies from MK2 knockout mice [67]. …”

Section: Chemokines In Healthmentioning

confidence: 99%

Chemokines in health and disease

Raman

Sobolik-Delmaire

Richmond

2011

Experimental Cell Research

324

223

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Chemokines and their receptors play a key role in development and homeostasis as well as in the pathogenesis of tumors and autoimmune diseases. Chemokines are involved in the implantation of the early conceptus, the migration of subsets of cells during embryonic development, and the overall growth of the embryo. Chemokines also have an important role in the development and maintenance of innate and adaptive immunity. In addition, they play a significant role in wound healing and angiogenesis. When the physiological role of chemokines is subverted or chronically amplified, disease often follows. Chemokines are involved in the pathobiology of chronic inflammation, tumorigenesis and metastasis, as well as autoimmune diseases. This article reviews the role of chemokines and their receptors in normal and disease processes and the potential for using chemokine antagonists for appropriate targeted therapy. Keywordschemokines; leukocytes; tumor progression; metastasis; autoimmune diseases Chemokines or chemotactic cytokines are a family of small molecular weight proteins that promote directional migration of leukocytes, endothelial and epithelial cells. Chemokines are classified into CXC, CC, CX 3 C or C chemokines based on the positioning of the conserved cysteine residues [1,2]. Based on their function, chemokines can be homeostatic, inflammatory, or both. Homeostatic chemokines are constitutively expressed and are important for many physiological processes, while the expression of inflammatory chemokines is induced by inflammatory stimuli. These small chemotactic proteins play a vital role in host defense mechanisms through development and maintenance of innate and acquired immunity. In addition to a role in immunity, they also regulate subsets of cells during embryogenesis. Importantly, chemokines are involved in wound healing, angiogenesis / angiostasis and in the development and metastasis of tumors.This review is organized into two major areas. In the first part of the review, the mechanism by which chemokines/chemokine receptors regulate chemotaxis will be discussed as well as their role in embryonic development, immunity, wound healing and angiogenesis. In the second part, the role of chemokines in inflammation and disease will be discussed.# Corresponding author: Dr. Ann Richmond, Ph. D., Dept. of Cancer Biology, 432 Preston Research Building, 23 rd Ave South @ Pierce, Vanderbilt University Medical Center, Nashville, TN 37232, ann.richmond@vanderbilt.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptExp Cell Res. Author man...

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MAPKAPK-2 Signaling Is Critical for Cutaneous Wound Healing

Cited by 44 publications

References 44 publications

LY2228820 Dimesylate, a Selective Inhibitor of p38 Mitogen-activated Protein Kinase, Reduces Angiogenic Endothelial Cord Formation in Vitro and in Vivo

LY2228820 Dimesylate, a Selective Inhibitor of p38 Mitogen-activated Protein Kinase, Reduces Angiogenic Endothelial Cord Formation in Vitro and in Vivo

An Insight into the Transcriptome of the Digestive Tract of the Bloodsucking Bug, Rhodnius prolixus

Chemokines in health and disease

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