Mechanical Stress Changes the Complex Interplay Between HO-1, Inflammation and Fibrosis, During Excisional Wound Repair
| Autor: | Niels A.J. Cremers, maarten esuttorp, marlous egerritsen, Ronald James Wong, Coby eVan Run-van Breda, gooitzen evan Dam, Katrien eBrouwer, Anne Marie eKuijpers-Jagtman, carine ecarels, Ditte eLundvig, Frank eWagener |
|---|---|
| Přispěvatelé: | Microbes in Health and Disease (MHD), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE) |
| Rok vydání: | 2015 |
| Předmět: |
Genetically modified mouse
musculoskeletal diseases Pathology medicine.medical_specialty wound healing Inflammation burns 03 medical and health sciences 0302 clinical medicine Dermis Fibrosis medicine Original Research 030304 developmental biology Skin repair 0303 health sciences lcsh:R5-920 Epidermis (botany) integumentary system business.industry General Medicine medicine.disease 3. Good health body regions Cleft Palate Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] burn wounds medicine.anatomical_structure Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] 030220 oncology & carcinogenesis Medicine Mechanical Stress medicine.symptom business Wound healing lcsh:Medicine (General) Myofibroblast Heme Oxygenase-1 Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] |
| Zdroj: | Frontiers in Medicine, 2 Frontiers in Medicine, Vol 2 (2015) Frontiers in Medicine Frontiers in Medicine, 2:86. Frontiers Media S.A. |
| ISSN: | 2296-858X |
| Popis: | Contains fulltext : 152467.pdf (Publisher’s version ) (Open Access) Mechanical stress following surgery or injury can promote pathological wound healing and fibrosis, and lead to functional loss and esthetic problems. Splinted excisional wounds can be used as a model for inducing mechanical stress. The cytoprotective enzyme heme oxygenase-1 (HO-1) is thought to orchestrate the defense against inflammatory and oxidative insults that drive fibrosis. Here, we investigated the activation of the HO-1 system in a splinted and non-splinted full-thickness excisional wound model using HO-1-luc transgenic mice. Effects of splinting on wound closure, HO-1 promoter activity, and markers of inflammation and fibrosis were assessed. After seven days, splinted wounds were more than three times larger than non-splinted wounds, demonstrating a delay in wound closure. HO-1 promoter activity rapidly decreased following removal of the (epi)dermis, but was induced in both splinted and non-splinted wounds during skin repair. Splinting induced more HO-1 gene expression in 7-day wounds; however, HO-1 protein expression remained lower in the epidermis, likely due to lower numbers of keratinocytes in the re-epithelialization tissue. Higher numbers of F4/80-positive macrophages, alphaSMA-positive myofibroblasts, and increased levels of the inflammatory genes IL-1beta, TNF-alpha, and COX-2 were present in 7-day splinted wounds. Surprisingly, mRNA expression of newly formed collagen (type III) was lower in 7-day wounds after splinting, whereas, VEGF and MMP-9 were increased. In summary, these data demonstrate that splinting delays cutaneous wound closure and HO-1 protein induction. The pro-inflammatory environment following splinting may facilitate higher myofibroblast numbers and increase the risk of fibrosis and scar formation. Therefore, inducing HO-1 activity against mechanical stress-induced inflammation and fibrosis may be an interesting strategy to prevent negative effects of surgery on growth and function in patients with orofacial clefts or in patients with burns. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|