ArticleMatrix biology : journal of the International Society for Matrix Biology2018
CCN4/WISP1 controls cutaneous wound healing by modulating proliferation, migration and ECM expression in dermal fibroblasts via α5β1 and TNFα.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 76 citations in OpenAlex.
- Effect of Plasma Gel on Viability, Proliferation and Migration of Dermal Human Fibroblasts In Vitro.Gels (Basel, Switzerland) · 2026Article
- Identification of a rare missense variant in the gene SPATA31H1 associated with hereditary gingival fibromatosis in a large Chinese family.BMC oral health · 2026Article
- The systemic wrinkled skin phenotype involves aberrant expression and variation of genes related to the oxidative stress and extracellular matrix in Xiang pigs.BMC genomics · 2025Article
- Serum Wnt1-Inducible signalling pathway Protein-1 levels are associated with cerebral infarction in patients with type 2 diabetes mellitus.Journal of endocrinological investigation · 2025Article
- Cell migration in diabetic wound healing: Molecular mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2025Review
- WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD.International journal of molecular sciences · 2024Review
- Matricellular proteins in immunometabolism and tissue homeostasis.BMB reports · 2024Review
- An overview of CCN4 (WISP1) role in human diseases.Journal of translational medicine · 2024Review
- Targeting Wnt/β-catenin signaling and its interplay with TGF-β and Notch signaling pathways for the treatment of chronic wounds.Cell communication and signaling : CCS · 2024Review
- WISP1 induces the expression of macrophage migration inhibitory factor in human lung fibroblasts through Src kinases and EGFR-activated signaling pathways.American journal of physiology. Cell physiology · 2024Article
- Human Serum Albumin/Selenium Complex Nanoparticles Protect the Skin from Photoaging Injury.International journal of nanomedicine · 2024Article
- Head-to-Head Comparison of CCN4, DNMT3A, PTPN11, and SPARC as Suppressors of Anti-tumor Immunity.Cellular and molecular bioengineering · 2023Article
- Article
- WNT1 Inducible Signaling Pathway Protein 1 Is a Stroma-Specific Secreting Protein Inducing a Fibroblast Contraction and Carcinoma Cell Growth in the Human Prostate.International journal of molecular sciences · 2022Article
- Altered regulation of mesenchymal cell senescence in adipose tissue promotes pathological changes associated with diabetic wound healing.Communications biology · 2022Article
- MBNL1 drives dynamic transitions between fibroblasts and myofibroblasts in cardiac wound healing.Cell stem cell · 2022Article
- Approaches for Regenerative Healing of Cutaneous Wound with an Emphasis on Strategies Activating the Wnt/β-Catenin Pathway.Advances in wound care · 2022Article
- WNT1-inducible signaling pathway protein 1 regulates kidney inflammation through the NF-κB pathway.Clinical science (London, England : 1979) · 2022Article
- Novel insights into negative pressure wound healing from an in situ porcine perspective.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2022Article
- Dedifferentiated Schwann cell-derived TGF-β3 is essential for the neural system to promote wound healing.Theranostics · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Understanding the mechanisms that control cutaneous wound healing is crucial to successfully manage repair of damaged skin. The goal of the current study was to uncover novel extracellular matrix (ECM) components that control the wound healing process. Full thickness skin defects were created in mice and used to show CCN4 up-regulation during wound-healing as early as 1 day after surgery, suggesting a role in inflammation and subsequent dermal migration and proliferation. To determine how CCN4 could regulate wound healing we used Ccn4-KO mice and showed they had delayed wound closure accompanied by reduced expression of Col1a1 and Fn mRNA. Boyden chamber assays using Ccn4-deficient dermal fibroblasts showed they have reduced migration and proliferation compared to WT counterparts. To confirm CCN4 has a role in proliferation and migration of dermal cells, siRNA knockdown and transduction of CCN4 adenoviral transduction were used and resulted in reduced or enhanced migration of human adult dermal fibroblast (hADF) cells respectively. The induced migration of the dermal fibroblasts by CCN4 appears to work via α5β1 integrin receptors that further stimulates down-stream ERK/JNK signaling. The regulation of CCN4 by TNF-α prompted us look further at their potential relationship. Treatment of hADFs with CCN4 and TNF-α alone or together showed CCN4 counteracted the inhibition of TNF-α on COL1A1 and FN mRNA expression and the stimulation of TNF-α on MMP-1 and MMP3 mRNA expression. CCN4 appeared to counterbalance the effects of TNF-α by inhibiting downstream NF-κB/p-65 signaling. Taken together we show CCN4 stimulates dermal fibroblast cell migration, proliferation and inhibits TNF-α stimulation, all of which could regulate wound healing.
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Registered trials
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.