High-Mobility Group Box 1 Protein in Human and Murine Skin: Involvement in Wound Healing

Straino, Stefania; Carlo, Anna Di; Mangoni, Antonella; Mori, Roberta De; Guerra, Liliana; Maurelli, Riccardo; Panacchia, Laura; Giacomo, Fabio Di; Palumbo, Roberta; Campli, C. Di; Uccioli, L.; Biglioli, Paolo; Bianchi, Marco E.; Capogrossi, Maurizio C.; Germani, Antonia

doi:10.1038/sj.jid.5701212

Cited by 145 publications

(175 citation statements)

References 42 publications

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“…Here, we demonstrate that extracellular HMGB1 promotes RPE cell migration by chemotaxis in vitro. This result is consistent with previous reports of HMGB1-induced cell migration in various cell types, such as smooth muscle cells, 21,33 fibroblasts, 45 and chondrocytes. 34 We also found that HMGB1 activated phosphorylation of ERK-1/2 in RPE cells and the migration induced by HMGB1 was dependent on ERK phosphorylation.…”

Section: Hmgb1 In Retinal Detachment N Arimura Et Alsupporting

confidence: 83%

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

Arimura

Kii

Hashiguchi

et al. 2009

Laboratory Investigation

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High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signalregulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.

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Section: Hmgb1 In Retinal Detachment N Arimura Et Alsupporting

confidence: 83%

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

Arimura

Kii

Hashiguchi

et al. 2009

Laboratory Investigation

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“…Straino, et al reported that HMGB1 levels of mice skin tissue were decreased in the diabetic state, and HMGB1 application to skin wounds promoted the tissue angiogenesis and wound healing. 36) Furthermore, Marchetti, et al proved that HMGB-1 was degraded by DPP4 in in vitro experiments and the inhibition of DPP4 enhanced tissue angiogenesis in a murine skin-wound model. 20) In the present study, we firstly demonstrated in vivo that cardio-protective effects, such as promotion of angiogenesis, suppression of cardiac remodeling, and enhancement of VEGF expression in the peri-infarct area, were reversed in diabetic state and ameliorated by administration of DPP4 inhibitor in the TG mice.…”

Section: Discussionmentioning

confidence: 99%

DPP4 Inhibition Ameliorates Cardiac Function by Blocking the Cleavage of HMGB1 in Diabetic Mice After Myocardial Infarction

et al. 2017

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SummaryHigh mobility group box 1 (HMGB1), a ubiquitous DNA-binding protein, promotes angiogenesis and tissue repair, resulting in restored cardiac function after myocardial infarction (MI). Although dipeptidyl peptidase 4 (DPP4) degrades certain peptides, it remains unclear as to whether HMGB1 is a substrate of DPP4 and whether DPP4 inhibition prevents the cleavage of HMGB1.In transgenic mice with cardiac-specific overexpression of HMGB1 (TG) and wild-type mice (WT), a diabetic state was induced by streptozotocin, and MI was created by ligation of the left anterior descending coronary artery. To inhibit DPP4 activity, a DPP4 inhibitor anagliptin was used. The plasma levels of HMGB1, infarct size, echocardiographic data, angiogenesis, and vascular endothelial growth factor (VEGF) expression in the peri-infarct area were compared among non-diabetic MI WT/TG, diabetic MI WT/TG, and anagliptin-treated diabetic MI WT/TG mice.DPP4 activity was increased in the diabetic state and blocked by anagliptin administration. The HMGB1 plasma levels were reduced in the diabetic TG compared with the non-diabetic TG mice, but DPP4 inhibition with anagliptin increased HMGB1 plasma levels in the diabetic TG mice. The infarct area was significantly larger in the diabetic TG than in the non-diabetic TG mice, and it was reduced by DPP4 inhibition. Cardiac function, angiogenesis, and VEGF expression were impaired in the diabetic TG mice, but they were ameliorated by the DPP4 inhibition to levels similar to those found in the non-diabetic TG mice.The DPP4 inhibitor ameliorated cardiac function by inhibiting the inactivation of HMGB1 in diabetic mice after MI.(Int Heart J 2017; 58: 778-786) Key words: Angiogenesis, Ischemic heart disease, Diabetes mellitus A cute myocardial infarction (MI) is an emergent disease caused by occlusion of the coronary artery. The morbidity and mortality of MI remain high despite the advancement of emergency medical services and the development of optimal therapies, including pharmacological treatment and percutaneous coronary intervention, and surgical technique. 1) Infarct size is known as an important prognostic predictor; thus, many studies of ischemic heart disease have been performed to determine how to limit the extent of infarction, focusing on the mechanisms of collateral development, ischemic reperfusion injury and ischemic preconditioning, among others. 2-4)High mobility group box 1 (HMGB1) is a ubiquitous non-histone DNA-binding protein that mediates gene transcription.5-7) HMGB1 secreted from necrotic cells into the extracellular space triggers tissue repair as a cytokine. [8][9][10][11] Moreover, several studies have proven that HMGB1 is involved in limiting the size of the infarct area and preserving cardiac function by promoting angiogenesis. 12,13) In addition, we have previously demonstrated that HMGB1 promotes angiogenesis and tissue repair by enhancing mobilization and differentiation of endothelial progenitor cells from bone marrow, resulting in preserving cardiac function after MI.14) Th...

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“…HMGB1 induces KC proliferation and migration via an unknown receptor. 84,85 HMGB1 activates the ERK1/2 pathway in KCs, and MEK inhibitors block the proliferative effect of HMGB1. 84 HMGB1 treatment increases the rate of wound closure in diabetic mice and retards the rate of wound closure in normal mice.…”

Section: 32mentioning

confidence: 99%

The Roles of Growth Factors in Keratinocyte Migration

Seeger

Paller

2015

Advances in Wound Care

152

114

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High-Mobility Group Box 1 Protein in Human and Murine Skin: Involvement in Wound Healing

Cited by 145 publications

References 42 publications

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

DPP4 Inhibition Ameliorates Cardiac Function by Blocking the Cleavage of HMGB1 in Diabetic Mice After Myocardial Infarction

The Roles of Growth Factors in Keratinocyte Migration

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