ArticleDiabetologia2012
High mobility group box 1 is a novel substrate of dipeptidyl peptidase-IV.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 52 citations in OpenAlex.
- The role of HMGB1 in vascular endothelial cells.Apoptosis : an international journal on programmed cell death · 2026Review
- Microbial dipeptidyl peptidases of the S9B family as host-microbe isozymes.Science advances · 2025Review
- Novel glucose-lowering agents that benefit diabetic foot: icing on the cake.Frontiers in endocrinology · 2025Review
- Review
- Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?International journal of molecular sciences · 2022Article
- Proline-specific peptidase activities (DPP4, PRCP, FAP and PREP) in plasma of hospitalized COVID-19 patients.Clinica chimica acta; international journal of clinical chemistry · 2022Article
- Influence of Dipeptidyl Peptidase-4 (DPP4) on Mesenchymal Stem-Cell (MSC) Biology: Implications for Regenerative Medicine - Review.Stem cell reviews and reports · 2022Review
- Review
- Cleavage of HMGB1 by Proteolytic Enzymes Associated with Inflammatory Conditions.Frontiers in immunology · 2020Article
- Dichotomous Role of Plasmin in Regulation of Macrophage Function after Acetaminophen Overdose.The American journal of pathology · 2019Article
- Ethyl Pyruvate Improves Pulmonary Function in Mice with Bleomycin-induced Lung Injury as Monitored with HyperpolarizedMagnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine · 2018Article
- [Research progress of dipeptidyl peptidase 4 inhibitors on healing of chronic diabetic foot ulcers].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2018Review
- The Vasculature in Prediabetes.Circulation research · 2018Review
- Alerting the body to tissue injury: The role of alarmins and DAMPs in cutaneous wound healing.Current pathobiology reports · 2018Article
- The pathological significance of dipeptidyl peptidase-4 in endothelial cell homeostasis and kidney fibrosis.Diabetology international · 2016Article
- Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence.International journal of molecular sciences · 2016Review
- The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice.Inflammation · 2016Article
- Dipeptidyl peptidase-4 and kidney fibrosis in diabetes.Fibrogenesis & tissue repair · 2016Review
- Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands.Scientific reports · 2015Article
- The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis.Frontiers in immunology · 2015Review
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11 authors at 4 institutions in 1 country.
Funding
Abstract
aims/hypothesisHigh mobility group box 1 (HMGB1) is a cytokine with a key role in tissue regeneration and angiogenesis. Previous studies have shown that topical application of HMGB1 to skin wounds of mouse models of diabetes enhanced vessel density and accelerated wound healing, suggesting that diabetes may affect endogenous HMGB1 functions. Dipeptidyl peptidase IV (DPP-IV/CD26) is a protease whose activity is increased in diabetes and whose inhibition improves glucose tolerance. Since HMGB1 contains potential DPP-IV cleavage sites, we determined whether HMGB1 may be a substrate for DPP-IV and whether DPP-IV-mediated cleavage may alter the biological activity of HMGB1.
methodsReversed phase HPLC, mass spectrometry and western blot analyses were performed to analyse and identify HMGB1 peptides generated following DPP-IV digestion. HMGB1 angiogenic functions in the presence of DPP-IV were evaluated in vitro and in vivo. HMGB1 protein was detected in the serum of type 2 diabetic patients before and after treatment with DPP-IV inhibitors.
resultsDPP-IV cleaved HMGB1 at its N-terminal region and affected its angiogenic functions. Specifically, DPP-IV inhibited HMGB1-induced endothelial cell migration and capillary-like structure formation, as well as HMGB1-mediated vascular network formation in Matrigel implants in mice. We had previously found that HMGB1 promoted endothelial cell migration through activation of extracellular regulated kinase signalling pathway. Here we showed that such an effect was abolished in the presence of DPP-IV. Finally, the N-terminal truncated form of HMGB1 was detected in the serum of type 2 diabetic patients, in whom DPP-IV inhibitors enhanced the levels of full-length HMGB1. CONCLUSIONS/
interpretationDPP-IV cleaves HMGB1 and, via this mechanism, inhibits HMGB1 angiogenic activity. Treatment with DPP-IV inhibitors may enhance HMGB1 activity in diabetic patients, thereby improving angiogenesis in this condition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.