2010
DOI: 10.2337/db09-1507
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High-Mobility Group Box-1 Protein Promotes Angiogenesis After Peripheral Ischemia in Diabetic Mice Through a VEGF-Dependent Mechanism

Abstract: OBJECTIVEHigh-mobility group box-1 (HMGB1) protein is a nuclear DNA-binding protein released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. Diabetic human and mouse tissues contain lower levels of HMGB1 than their normoglycemic counterparts. Deficient angiogenesis after ischemia contributes to worse outcomes of peripheral arterial disease in patients with diabetes. To test the hypothesis that HMGB1 enhances ischemia-induced angiogenesis in diabetes, we admini… Show more

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Cited by 110 publications
(123 citation statements)
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“…We previously reported increased levels of HMGB1 in asthma patients and asthmatic mice. 7,8 In this study, we present additional evidence that HMGB1 may be involved in the pathogenesis of asthma, including airway remodeling. Our finding that anti-HMGB1 treatment inhibits airway remodeling in a mouse model of chronic asthma is consistent with a recent report by Lee et al 19 However, our study identified a different mechanism.…”
Section: Discussionmentioning
confidence: 58%
See 1 more Smart Citation
“…We previously reported increased levels of HMGB1 in asthma patients and asthmatic mice. 7,8 In this study, we present additional evidence that HMGB1 may be involved in the pathogenesis of asthma, including airway remodeling. Our finding that anti-HMGB1 treatment inhibits airway remodeling in a mouse model of chronic asthma is consistent with a recent report by Lee et al 19 However, our study identified a different mechanism.…”
Section: Discussionmentioning
confidence: 58%
“…More interestingly, HMGB1 has been shown to play a pivotal role in pulmonary fibrosis, partly through reduction of fibroblast proliferation and downregulation of interleukin (IL)-1b levels. 7 Furthermore, some researchers have found that HMGB1 promotes secretion of vascular endothelial growth factor (VEGF) 8 and that treatment with anti-HMGB1 antibodies suppresses the activity of matrix metalloproteinase (MMP)-9, 9 both of which are involved in airway remodeling.…”
Section: Introductionmentioning
confidence: 99%
“…We divided the mice into six groups; control MI groups (WT and TG), diabetic MI groups (WT-DM and TG-DM), and diabetic MI treated with DPP 4 inhibitor groups (WT-DM-DPP4I and TG-DM-DPP4I). To induce a diabetic state, streptozotocin (STZ, 50 mg/kg/ day, Sigma, St. Louis, MO, USA), which was dissolved in 0.1 M sodium citrate buffer (pH 4.5) as described in previous reports, 21) was administered for five consecutive days by intraperitoneal injection. Sodium citrate buffer without STZ was administered to control MI group for five consecutive days by intraperitoneal injection.…”
Section: Animals and Ethical Statementsmentioning
confidence: 99%
“…[69][70][71][72] In addition, HMGB1 is reported to possess proangiogenic activity. [73][74][75][76] Its ability to promote proliferation, migration, and differentiation of several cell types, particularly those involved in angiogenesis, prompted us to examine the ability of HMGB1 to mobilize EPCs from the bone marrow. We observed significant mobilization of bone marrow EPCs and their initial sequestration in the spleen.…”
Section: Systemic Inflammation: Three Waves Of Danger Signalingmentioning
confidence: 99%