ArticlePloS one2012
Targeting Cx43 and N-cadherin, which are abnormally upregulated in venous leg ulcers, influences migration, adhesion and activation of Rho GTPases.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 61 citations in OpenAlex.
- The effect of a connexin43-based Peptide on the healing of chronic venous leg ulcers: a multicenter, randomized trial.The Journal of investigative dermatology · 2015Trial
- Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells.Cell and tissue research · 2026Article
- Connexin 43 expression in irradiated human neck skin: a prospective case-control study.Annals of translational medicine · 2025Article
- Cx43 mediates changes in myofibroblast contraction and collagen release in human amniotic membrane defects after trauma.Scientific reports · 2021Article
- Epidermal graft encourages wound healing by down-regulation of gap junctional protein and activation of wound bed without graft integration as opposed to split-thickness skin graft.International wound journal · 2021Article
- Changes in connexin 43 in inflammatory skin disorders: Eczema, psoriasis, and Steven-Johnson syndrome/toxic epidermal necrolysis.Health science reports · 2021Article
- Cx43 and Associated Cell Signaling Pathways Regulate Tunneling Nanotubes in Breast Cancer Cells.Cancers · 2020Article
- Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-Oxidative medicine and cellular longevity · 2020Article
- Article
- Gap Junctions and Wnt Signaling in the Mammary Gland: a Cross-Talk?Journal of mammary gland biology and neoplasia · 2019Review
- The Role of Connexin-43 in the Inflammatory Process: A New Potential Therapy to Influence Keratitis.Journal of ophthalmology · 2019Review
- Connexin 43-Based Therapeutics for Dermal Wound Healing.International journal of molecular sciences · 2018Review
- Connexin 30 controls astroglial polarization during postnatal brain development.Development (Cambridge, England) · 2018Article
- The Connexin Mimetic Peptide Gap27 and Cx43-Knockdown Reveal Differential Roles for Connexin43 in Wound Closure Events in Skin Model Systems.International journal of molecular sciences · 2018Article
- Trauma induces overexpression of Cx43 in human fetal membrane defects.Prenatal diagnosis · 2017Article
- Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice.Cell death & disease · 2017Article
- Connexin 43: Key roles in the skin.Biomedical reports · 2017Article
- The assembly of developing motor neurons depends on an interplay between spontaneous activity, type II cadherins and gap junctions.Development (Cambridge, England) · 2017Article
- Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia.Molecular biology of the cell · 2016Article
- The Role of Connexins in Wound Healing and Repair: Novel Therapeutic Approaches.Frontiers in physiology · 2016Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVenous leg ulcers can be very hard to heal and represent a significant medical need with no effective therapeutic treatment currently available. PRINCIPAL
findingsIn wound edge biopsies from human venous leg ulcers we found a striking upregulation of dermal N-cadherin, Zonula Occludens-1 and the gap junction protein Connexin43 (Cx43) compared to intact skin, and in stark contrast to the down-regulation of Cx43 expression seen in acute, healing wounds. We targeted the expression of these proteins in 3T3 fibroblasts to evaluate their role in venous leg ulcers healing. Knockdown of Cx43 and N-cadherin, but not Zonula Occludens-1, accelerated cell migration in a scratch wound-healing assay. Reducing Cx43 increased Golgi reorientation, whilst decreasing cell adhesion and proliferation. Furthermore, Connexin43 and N-cadherin knockdown led to profound effects on fibroblast cytoskeletal dynamics after scratch-wounding. The cells exhibited longer lamelipodial protrusions lacking the F-actin belt seen at the leading edge in wounded control cells. This phenotype was accompanied by augmented activation of Rac-1 and RhoA GTPases, as revealed by Förster Resonance Energy Transfer and pull down experiments.
conclusionsCx43 and N-cadherin are potential therapeutic targets in the promotion of healing of venous leg ulcers, by acting at least in part through distinct contributions of cell adhesion, migration, proliferation and cytoskeletal dynamics.
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