ArticleCell communication and signaling : CCS2019
Elevated Kallikrein-binding protein in diabetes impairs wound healing through inducing macrophage M1 polarization.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
- The Role of the Notch1 Signaling Pathway in the Pathogenesis and Treatment of Diabetic Foot: A Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Review
- ATF7 drives diabetic wound healing via NOTCH1 repression and N1ICD-dependent macrophage polarization control.JCI insight · 2026Article
- Salidroside-loaded stem cell-derived artificial nanovesicles in hydrogel microneedles alleviate inflammation and enhance diabetic wound regeneration.Materials today. Bio · 2026Article
- Elevated Kallistatin Induces Myosteatosis and Exercise Intolerance by Antagonizing AdipoR1-Mediated AMPK Signalling.Journal of cachexia, sarcopenia and muscle · 2026Article
- Insights Into Macrophage Polarization and M1/M2 Balance in Diabetic Foot Ulcers.Journal of diabetes · 2026Review
- Revolutionizing Diabetic Foot Ulcer Management: Exploring the Therapeutic Potential of Natural Products.Current pharmaceutical design · 2026Review
- Histone post-translational modifications in diabetic foot ulcer healing: linking immune dysregulation to tissue repair.Frontiers in immunology · 2026Review
- Fueling bone loss: the immunometabolic reprogramming of the bone microenvironment in diabetic osteoporosis.Frontiers in immunology · 2026Review
- Multimodal Bioactive Approaches in Smart Dressings for Diabetic Foot Ulcers.International journal of nanomedicine · 2026Review
- Immune cells in diabetic wound repair: the key to better wound management.Frontiers of medicine · 2025Review
- Harnessing 3D cultured MSC exosomes through tangential flow filtration for enhanced diabetic wound healing.Stem cells translational medicine · 2025Article
- Cascade-targeting pH/ROS microneedles promote scarless diabetic wound healing by macrophage metaboimmune reprogramming.Science advances · 2025Article
- Article
- Dibenzazepine, a γ-Secretase Enzyme Inhibitor, Protects Against Doxorubicin-Induced Cardiotoxicity by Suppressing NF-κB, iNOS, and Hes1/Hey1 Expression.Inflammation · 2025Article
- Exosomes from MicroRNA-125b-Modified Adipose-Derived Stem Cells Promote Wound Healing of Diabetic Foot Ulcers.Current stem cell research & therapy · 2025Article
- The multifaceted role of kallistatin in human diseases: mechanistic insights and translational potential.Frontiers in cardiovascular medicine · 2025Review
- GelMA loaded with exosomes from human minor salivary gland organoids enhances wound healing by inducing macrophage polarization.Journal of nanobiotechnology · 2024Article
- Understanding and treating diabetic foot ulcers: Insights into the role of cutaneous microbiota and innovative therapies.Skin health and disease · 2024Review
- Blocking group 2 innate lymphoid cell activation and macrophage M2 polarization: potential therapeutic mechanisms in ovalbumin-induced allergic asthma by calycosin.BMC pharmacology & toxicology · 2024Article
- Review
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe accumulation of M1-polarized macrophages and excessive inflammation are important in the pathogenesis of diabetic foot ulcer (DFU). However, the underlying mechanism of DFU pathogenesis and the crucial regulators of DFU are less well known. Our previous study reported that kallikrein-binding protein (KBP), an angiogenesis inhibitor, was significantly upregulated in diabetic patients compared to its levels in controls. The effects of KBP on monocyte chemotaxis and macrophage M1 polarization were elucidated in this study.
methodsPlasma KBP levels and monocyte counts were assessed by ELISA and flow cytometry. Wound closure rates in different groups were monitored daily. The phenotype and recruitment of macrophages were measured by real-time PCR, western blot and immunofluorescence assays. The expression of Notch and NF-κB signalling pathway members was determined by the methods mentioned above. ChIP and dual-luciferase reporter gene assays were employed to explore the binding and transcriptional regulation of Hes1 and iNOS.
resultsWe found that plasma KBP levels and circulating monocytes were elevated in diabetic patients compared to those in nondiabetic controls, and both were higher in diabetic patients with DFU than in diabetic patients without DFU. KBP delayed wound healing in normal mice; correspondingly, KBP-neutralizing antibody ameliorated delayed wound healing in diabetic mice. Circulating monocytes and macrophage infiltration in the wound were upregulated in KBP-TG mice compared to those in control mice. KBP promoted the recruitment and M1 polarization of macrophages. Mechanistically, KBP upregulated iNOS by activating the Notch1/RBP-Jκ/Hes1 signalling pathway. Hes1 downregulated CYLD, a negative regulator of NF-κB signalling, and then activated the IKK/IκBα/NF-κB signalling pathway.
conclusionsOur findings demonstrate that KBP is the key regulator of excessive inflammation in DFUs and provide a novel target for DFU therapy.
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