Differential expression of tissue inhibitors of metalloproteinases (TIMP-1, -2, -3, and -4) in normal and aberrant wound healing
| Autor: | Ulpu Saarialho-Kere, Tomi Leivo, Maarit Vaalamo |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Keratinocytes
Pathology medicine.medical_specialty Stromal cell Time Factors Angiogenesis Biology Matrix metalloproteinase Epithelium Pathology and Forensic Medicine Extracellular matrix 03 medical and health sciences 0302 clinical medicine Skin Ulcer medicine Humans RNA Messenger Enzyme Inhibitors In Situ Hybridization 030304 developmental biology Aged Skin Basement membrane Aged 80 and over Tissue Inhibitor of Metalloproteinase-3 0303 health sciences Tissue Inhibitor of Metalloproteinase-2 Wound Healing Tissue Inhibitor of Metalloproteinase-1 integumentary system Epidermis (botany) Granulation tissue Tissue Inhibitor of Metalloproteinases Middle Aged Immunohistochemistry medicine.anatomical_structure 030220 oncology & carcinogenesis Wound healing |
| Zdroj: | Human pathology. 30(7) |
| ISSN: | 0046-8177 |
| Popis: | Wound healing is characterized by hemostasis, re-epithelialization, granulation tissue formation, and remodeling of the extracellular matrix. Matrix metalloproteinases and their specific inhibitors, TIMPs, contribute to these events. We investigated a total of 47 samples of normally healing wounds, chronic venous ulcers, ulcerative vasculitis, and suction blisters using immunohistochemistry and in situ hybridization, to clarify the role of TIMPs in normal and aberrant wound repair. Expression of TIMP-1 and -3 mRNAs was found in proliferating keratinocytes in 3- to 5-day-old normally healing wounds, whereas no epidermal expression was detected in chronic ulcers. However, TIMP-3 protein was found in the proliferating epidermis in 20 of 24 samples representing both full-thickness acute and chronic wounds. TIMP-1 and TIMP-3 also were abundantly expressed by spindle-shaped, fibroblast-like, and plump, macrophage-like stromal cells, as well as by endothelial cells. In normally healing wounds, TIMP-2 protein localized under the migrating epithelial tip and to the stromal tissue under the eschar more frequently than in chronic ulcers. Occasional staining for TIMP-4 protein was detected in stromal cells of chronic ulcers near blood vessels. Our results indicate that TIMP-1 and TIMP-3 may be involved both in the regeneration of the epidermis by stabilizing the basement membrane zone and in the regulation of stromal remodeling and angiogenesis of the wound bed. Lack of TIMP-2 near the migrating epithelial wound edges might contribute to uncontrolled activity of MMP-2 in chronic ulcers. We conclude also that TIMPs are temporally and spatially tightly regulated and that the imbalance between metalloproteinases and TIMPs-1, -2, and -3 may lead to delayed wound healing. |
| Databáze: | OpenAIRE |
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