Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis
| Autor: | Daniele Bergeron, Sébastien Larochelle, Alexis Armour, Carlos A. Lopez-Vallé, Franck Simon, Véronique J. Moulin, Hervé Genest |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Keratinocytes
Pathology medicine.medical_specialty Cicatrix Hypertrophic Human skin Enzyme-Linked Immunosorbent Assay Matrix (biology) Matrix metalloproteinase Critical Care and Intensive Care Medicine Extracellular matrix Hypertrophic scar Fibrosis Medicine Humans Electrophoresis Gel Two-Dimensional Cells Cultured Wound Healing Tissue Inhibitor of Metalloproteinase-1 Epidermis (botany) business.industry General Medicine Anatomy medicine.disease Immunohistochemistry medicine.anatomical_structure Culture Media Conditioned Emergency Medicine Surgery business Keratinocyte |
| Zdroj: | Burns : journal of the International Society for Burn Injuries. 38(3) |
| ISSN: | 1879-1409 |
| Popis: | Hypertrophic scars are a pathological process characterized by an excessive deposition of extracellular matrix components. Using a tissue-engineered reconstructed human skin (RHS) method, we previously reported that pathological keratinocytes induce formation of a fibrotic dermal matrix. We further investigated keratinocyte action using conditioned media. Results showed that conditioned media induce a similar action on dermal thickness similar to when an epidermis is present. Using a two-dimensional electrophoresis technique, we then compared conditioned media from normal or hypertrophic scar keratinocytes and determined that TIMP-1 was increased in conditioned media from hypertrophic scar keratinocytes. This differential profile was confirmed using ELISA, assaying TIMP-1 presence on media from monolayer cultured keratinocytes and from RHS. The dermal matrix of these RHS was recreated using mesenchymal cells from three different origins (skin, wound and hypertrophic scar). The effect of increased TIMP-1 levels on dermal fibrosis was also validated independently from the mesenchymal cell origin. Immunodetection of TIMP-1 showed that this protein was increased in the epidermis of hypertrophic scar biopsies. The findings of this study represent an important advance in understanding the role of keratinocytes as a direct potent modulator for matrix degradation and scar tissue remodeling, possibly through inactivation of MMPs. |
| Databáze: | OpenAIRE |
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