Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis
Simon F et al. – 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.Methods
- Hypertrophic scars are a pathological process characterized by an excessive deposition of extracellular matrix components.
- Using a tissue-engineered reconstructed human skin (RHS) method, the authors previously reported that pathological keratinocytes induce formation of a fibrotic dermal matrix.
- They 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, the authors 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.