Keratinocyte regulation of TGF-beta and connective tissue growth factor expression: a role in suppression of scar tissue formation.
Allogeneic keratinocytes applied to large full-thickness wounds promote healing while suppressing scar tissue formation. This effect may be mediated in part by their effect on the levels of transforming growth factor-betas (TGF-betas) and connective tissue growth factor (CTGF) in the wound and subsequent modulation of fibroblast activity. We have examined the levels of TGF-beta and CTGF produced by keratinocytes and fibroblasts, and the effect of keratinocyte-conditioned medium using monolayer and living skin-equivalent cultures. Keratinocyte monolayers did not release any detectable TGF-beta1, but released moderate levels of TGF-beta2 into culture medium, and stained strongly for TGF-beta1, but only weakly for TGF-beta2. Fibroblasts released large amounts of TGF-beta1, no TGF-beta2, and stained strongly for TGF-beta1. Neither cell type released TGF-beta3, but both stained strongly for TGF-beta3. Keratinocyte-conditioned medium suppressed the levels of TGF-betas and CTGF associated with the fibroblasts compared with fibroblasts incubated in Dulbecco's minimal essential medium and fibroblast-conditioned medium. In living skin equivalents, keratinocytes stained very strongly for TGF-beta1 and CTGF, moderately strongly for TGF-beta3, and only weakly for TGF-beta2. Fibroblasts stained strongly for TGF-beta1 and 3 and CTGF. These observations suggest that keratinocytes may affect the TGF-beta profile in such a way as to suppress the formation of scar tissue.
Amjad
Syed Basith
SB
University Department of Surgical Paediatrics, Royal Hospital for Sick Children, Yorkhill, Glasgow, United Kingdom.
Carachi
Robert
R
Edward
Michael
M
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000503:physiopathology*; D055513:Connective Tissue Growth Factor; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology*; D051381:Rats; D012867:Skin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor