Targeted inhibition of endothelial calpain delays wound healing by reducing inflammation and angiogenesis
| Autor: | Zhenya Shen, Chenlong Yi, Dong Zheng, Xiaomei Teng, Haoyue Huang, Guangying Peng, Weihua Wu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD31 Cancer Research Angiogenesis Immunology Inflammation Cellular imaging Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Genetic model medicine Animals Humans lcsh:QH573-671 Cell Proliferation Skin repair Tube formation Wound Healing biology Neovascularization Pathologic lcsh:Cytology Chemistry Calpain Cell Biology Cell biology 030104 developmental biology 030220 oncology & carcinogenesis biology.protein medicine.symptom Wound healing |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 7, Pp 1-12 (2020) |
| ISSN: | 2041-4889 |
| Popis: | Wound healing is a multistep phenomenon that relies on complex interactions between various cell types. Calpains are a well-known family of calcium-dependent cysteine proteases that regulate several processes, including cellular adhesion, proliferation, and migration, as well as inflammation and angiogenesis. CAPNS1, the common regulatory subunit of Calpain-1 and 2, is indispensable for catalytic subunit stabilization and activity. Calpain inhibition has been shown to reduce organ damage in various disease models. Here, we report that endothelial calpain-1/2 is crucially involved in skin wound healing. Using a mouse genetic model where Capns1 is deleted only in endothelial cells, we showed that calpain-1/2 disruption is associated with reduced injury-activated inflammation, reduced CD31+ blood vessel density, and delayed wound healing. Moreover, in cultured HUVECs, inhibition of calpain reduced TNF-α-induced proliferation, migration, and tube formation. Deletion of Capns1 was associated with elevated levels of IκB and downregulation of β-catenin expression in endothelial cells. These observations delineate a novel mechanistic role for calpain in the crosstalk between inflammation and angiogenesis during skin repair. |
| Databáze: | OpenAIRE |
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