ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
CaMKK2 Regulates Macrophage Polarization Induced by Matrix Stiffness: Implications for Shaping the Immune Response in Stiffened Tissues.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Mechano-immunomodulatory biomaterials: From immune mechanosensing to translational design.Bioactive materials · 2026Review
- A Hybrid Hierarchical Framework for Quantifying Mechanical Markers in Atherosclerotic Disease Progression: A New Approach for Diagnosis and Risk Assessment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Stromal cell-mediated tuning of the extracellular matrix for immune tissue engineering.Current opinion in biomedical engineering · 2026Article
- Regulating Cells Fate and Function to Facilitate Bone Regeneration via Designing Programmable Bio-Interactive Materials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cardiac immunity and heart repair: Mechanism, challenge, and future direction.Chinese medical journal · 2026Review
- Nanomedicine targeting ECM stiffness: restoring mechanical homeostasis for cancer immunotherapy.Materials today. Bio · 2026Review
- Article
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Mechanical regulation of microenvironment remodeling in brain tumors: from mechanism to therapy.Journal of neuroinflammation · 2026Review
- High-throughput bioprinted 3D cultures for probing host-pathogen interactions in bioinspired microenvironments.RSC applied polymers · 2026Article
- Novel AI-Driven Precision Strategies in Diabetic Wound Healing: Immunomodulation and Advances in Smart Composite Nanocarriers.Pharmaceutics · 2026Review
- Quantifying Information Exchange Between Cells in Inflammaging.Bioengineering (Basel, Switzerland) · 2026Article
- Hemodynamics and matrix stiffness shape the pathogenicity of SPP1Frontiers in immunology · 2026Review
- Sequential polarization of macrophages: an immunomodulatory strategy for novel bone repair materials.Regenerative biomaterials · 2026Review
- Targeting macrophage function with botulinum toxin: a novel translational strategy for preventing and treating pathological scars.Postepy dermatologii i alergologii · 2026Review
- Mechanoresponsive reprogramming of tumor-associated macrophages during cancer progression.Frontiers in cell and developmental biology · 2026Review
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- Microfluidic engineering of immune-competent organs-on-chips and their applications.Frontiers in immunology · 2026Review
- Targeting delayed healing tissues: immune reprogramming of adaptive immune cells by biomaterials.Regenerative biomaterials · 2026Review
- A matrix stiffness gene signature identifies SLC20A1 as a novel mechano-immunological checkpoint enabling synergistic immunotherapy in pancreatic ductal adenocarcinoma.Cancer immunology, immunotherapy : CII · 2025Article
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Authors and funding
8 authors.
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Abstract
Macrophages are essential for immune responses and maintaining tissue homeostasis, exhibiting a wide range of phenotypes depending on their microenvironment. The extracellular matrix (ECM) is a vital component that provides structural support and organization to tissues, with matrix stiffness acting as a key regulator of macrophage behavior. Using physiologically relevant 3D stiffening hydrogel models, it is found that increased matrix stiffness alone promoted macrophage polarization toward a pro-regenerative phenotype, mimicking the effect of interleukin-4(IL-4) in softer matrices. Blocking Calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) selectively inhibited stiffness-induced macrophage polarization without affecting IL-4-driven pro-regenerative pathways. In functional studies, CaMKK2 deletion prevented M2-like/pro-tumoral polarization caused by matrix stiffening, which in turn hindered tumor growth. In a murine wound healing model, loss of CaMKK2 impaired matrix stiffness-mediated macrophage accumulation, ultimately disrupting vascularization. These findings highlight the critical role of CaMKK2 in the macrophage mechanosensitive fate determination and gene expression program, positioning this kinase as a promising therapeutic target to selectively modulate macrophage responses in pathologically stiff tissues.
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Registered trials
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