Calpain Activity Is Essential in Skin Wound Healing and Contributes to Scar Formation
| Autor: | Selim Aractingi, Kiarash Khosrotehrani, Laurent Baud, Dany Nassar, Emmanuel Letavernier |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Skin Physiology
Pathology Anatomy and Physiology Mouse Angiogenesis lcsh:Medicine Mice Cell Movement Fibrosis Integrative Physiology Molecular Cell Biology Homeostasis Myofibroblasts lcsh:Science Cells Cultured Skin Skin repair Multidisciplinary biology Calpain Granulation tissue Cell Differentiation Animal Models Cell biology Platelet Endothelial Cell Adhesion Molecule-1 medicine.anatomical_structure Female Collagen medicine.symptom Myofibroblast Research Article Cell Physiology medicine.medical_specialty Histology Mice Transgenic Inflammation Cicatrix Model Organisms Cell Adhesion medicine Animals Humans Biology Wound Healing Calcium-Binding Proteins lcsh:R Fibroblasts medicine.disease Actins Mice Inbred C57BL Granulation Tissue biology.protein Blood Vessels lcsh:Q Physiological Processes Wound healing |
| Zdroj: | PLoS ONE, Vol 7, Iss 5, p e37084 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Wound healing is a multistep phenomenon that relies on complex interactions between various cell types. Calpains are ubiquitously expressed proteases regulating several processes including cellular adhesion and motility as well as inflammation and angiogenesis. Calpains can be targeted by inhibitors, and their inhibition was shown to reduce organ damage in various disease models. We aimed to assess the role of calpains in skin healing and the potential benefit of calpain inhibition on scar formation. We used a pertinent model where calpain activity is inhibited only in lesional organs, namely transgenic mice overexpressing calpastatin (CPST), a specific natural calpain inhibitor. CPST mice showed a striking delay in wound healing particularly in the initial steps compared to wild types (WT). CPST wounds displayed reduced proliferation in the epidermis and delayed re-epithelization. Granulation tissue formation was impaired in CPST mice, with a reduction in CD45+ leukocyte infiltrate and in CD31+ blood vessel density. Interestingly, wounds on WT skin grafted on CPST mice (WT/CPST) showed a similar delayed healing with reduced angiogenesis and inflammation compared to wounds on WT/WT mice demonstrating the implication of calpain activity in distant extra-cutaneous cells during wound healing. CPST wounds showed a reduction in alpha-smooth muscle actin (αSMA) expressing myofibroblasts as well as αSMA RNA expression suggesting a defect in granulation tissue contraction. At later stages of skin healing, calpain inhibition proved beneficial by reducing collagen production and wound fibrosis. In vitro, human fibroblasts exposed to calpeptin, a pan-calpain inhibitor, showed reduced collagen synthesis, impaired TGFβ-induced differentiation into αSMA-expressing myofibroblasts, and were less efficient in a collagen gel contraction assay. In conclusion, calpains are major players in granulation tissue formation. In view of their specific effects on fibroblasts a late inhibition of calpains should be considered for scar reduction. |
| Databáze: | OpenAIRE |
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