title: Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis.
abstract: 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.
authors: Centre LOEX de l'Université Laval, Génie Tissulaire et Régénération: LOEX du Centre de Recherche FRSQ du Centre Hospitalier affilié Universitaire de Québec, Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors: Franck
authors: F
authors: Simon
authors: Daniele
authors: D
authors: Bergeron
authors: Sébastien
authors: S
authors: Larochelle
authors: Carlos A
authors: CA
authors: Lopez-Vallé
authors: Hervé
authors: H
authors: Genest
authors: Alexis
authors: A
authors: Armour
authors: Véronique J
authors: VJ
authors: Moulin
mesh_terms: D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000201:enzymology* / Q000473:pathology; D017077:Culture Media, Conditioned; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000201:enzymology* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D019715:Tissue Inhibitor of Metalloproteinase-1