Keratinocyte-conditioned media regulate collagen expression in dermal fibroblasts.
Excessive extracellular matrix (ECM) production during dermal wound healing often leads to fibrotic conditions such as keloids and hypertrophic scarring (HSc). Type I collagen is the predominant form of collagen in the human skin and is produced mainly by dermal fibroblasts. It has been suggested that abnormalities in epidermal-dermal interaction can lead to excessive production of collagen by fibroblasts. To identify and further characterize any possible keratinocyte-derived collagen-inhibitory factors (KD-CIFs), we investigated the expression of pro-alpha1(I) collagen at the level of mRNA and protein in human fibroblasts that had been either co-cultured with keratinocytes or treated with keratinocyte-conditioned medium (KCM). Fibroblasts in both groups demonstrated a significant reduction in the steady-state levels of collagen mRNA and protein. Further characterization of KD-CIFs revealed a high-molecular-weight factor (>30 kDa) that showed stable activity at high temperature (56 degrees C) and acidic pH (pH 2). Keratinocyte differentiation did not alter the release of KD-CIFs into KCM. These results provide further evidence that type I collagen expression and synthesis in fibroblasts are regulated by a keratinocyte-releasable factor(s) with an apparent molecular weight between 30 and 50 kDa.
Ghaffari
Abdi
A
Department of Surgery, BC Professional Firefighter's Burn and Wound Healing Research Lab, University of British Columbia, Vancouver, British Columbia, Canada.
Kilani
Ruhangiz T
RT
Ghahary
Aziz
A
D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D020405:Dermis / Q000166:cytology*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism
D024042:Collagen Type I; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D020781:Matrix Metalloproteinase 1