ArticleCell biology and toxicology2023
WDR74 facilitates TGF-β/Smad pathway activation to promote M2 macrophage polarization and diabetic foot ulcer wound healing in mice.
Article in Cell biology and toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 89 citations in OpenAlex.
- Neoplastic CD3⁺ B cells remodel the DLBCL tumor microenvironment via single-cell and spatial transcriptomics.Cancer biology & therapy · 2026Article
- MAFB Overexpression in Macrophages Promotes Wound Healing in Diabetic Foot Ulcer by Transcriptionally Activating WDR74 to Drive a Tissue-Repair Phenotype and Suppress Inflammation and Oxidative Stress.Applied biochemistry and biotechnology · 2026Article
- Discovery of FBP1 as novel therapeutic target and asiatic acid-hydrogen sulfide donors accelerate diabetic wound healing.Journal of advanced research · 2026Article
- Macrophage-Derived Extracellular Vesicles Deliver Progranulin to Alleviate Skin Wound Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Advances in Chinese herbal medicine for diabetic wound treatment: from tradition to innovation.Chinese medicine · 2026Review
- MMT: A Potential Mechanism of Myocardial Fibrosis - Regulation of the TGF-β1/Smad3 Pathway and Prospects for Targeted Therapy.Reviews in cardiovascular medicine · 2026Review
- Macrophage Derived TGF-β Recruits BMSCs for Initiation of Bone Formation During Fracture Healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Multi-omics integration identifies macrophage senescence driven by the RUNX1-P53 axis as a key mechanism in diabetic foot ulcer.Functional & integrative genomics · 2026Article
- Integrated multi-technology exploration of the mechanism by which Badushengji San regulates core targets in diabetic foot ulcer.Molecular genetics and genomics : MGG · 2026Article
- Inflammation and wound healing: a comprehensive overview of mechanisms, therapeutic strategies, and translational perspectives.Biomarker research · 2026Review
- Transcriptional and ubiquitinative suppression of macrophage CST3 disrupts colonic homeostasis through defective efferocytosis.Cell death and differentiation · 2026Article
- Mechanisms of IL-17A Neutralisation in Alleviating Renal Fibrosis and Inflammation in Spontaneously Hypertensive Rats.Clinical and experimental pharmacology & physiology · 2026Article
- Microneedle Strategies for Diabetic Wound Management: A Comprehensive Review of Materials, Mechanisms, and Therapeutic Outcomes.Materials today. Advances · 2026Article
- Emodin: A Promising Natural Compound for Combating Fibrotic Diseases.Current medical science · 2026Review
- Danshen/Huanglian-loaded gelatin/Bletilla striata gum dressings accelerate wound healing in anal fistula by promoting angiogenesis through TGF-β/Smad pathway activation.Journal of molecular histology · 2026Article
- Beyond wound closure: translational opportunities and barriers of mesenchymal stem cells and their extracellular vesicles in burn management.Frontiers in cell and developmental biology · 2026Review
- Article
- Single-cell omics reveals arg-1 as a key regulator of age-dependent macrophage-mediated cartilage repair.PloS one · 2026Article
- From inflammatory activation to fibrotic remodeling: the central role of macrophage heterogeneity in frozen shoulder.Frontiers in immunology · 2026Review
- CORO1A links inflammatory chondrocyte subpopulations to immune microenvironment alterations in osteoarthritis: an integrative multi-omics and single-cell study.Frontiers in immunology · 2026Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic foot ulcer (DFU) is a devastating component of diabetes progression, leading to decreased quality of life and increased mortality in diabetic patients. The underlying mechanism of DFU is not completely understood. Hence, this study aims to elucidate the mechanism involved in wound healing in mouse models of DFU. Gain- and loss-of-function studies were performed to study the roles that WDR74 and TGF-β play in mouse models of DFU and primary bone marrow-derived mouse macrophages. M1 and M2 macrophage phenotypic markers, extracellular matrix (ECM) components, and angiogenic makers were determined by RT-qPCR and/or Western blot analysis. Localization of these proteins was determined by immunofluorescence staining and/or immunohistochemistry. Interaction between WDR74 with Smad2/3 in macrophages was detected by co-immunoprecipitation. We found that WDR74 and M2 macrophages were decreased in wound tissues from DFU mice. TGF-β/Smad pathway activation increased the expression of M2 macrophage markers (arginase-1 and YM1), IL-4, while decreased expression of M1 macrophage marker (iNOS). TGF-β/Smad pathway activation also increased the production of ECM and promoted the wound closure in diabetic mice. We also noticed that WDR74 overexpression increased Smad2/3 phosphorylation, elevated the population of M2 macrophage and ECM production, and alleviated DFU. LY2109761 treatment normalized effects of TGF-β or WDR74 overexpression. In conclusion, WDR74 promoted M2 macrophage polarization, leading to improved DFU in mice, through activation of the TGF-β/Smad pathway. Graphical Headlights 1. WDR74 promotes M2 macrophage polarization and ECM production. 2. WDR74 activates the TGF-β/Smad signaling pathway. 3. TGF-β/Smad activation promotes M2 macrophage polarization in murine DFU. 4. WDR74 enhances wound healing in murine DFU.
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