Secreted Factors from Keloid Keratinocytes Modulate Collagen Deposition by Fibroblasts from Normal and Fibrotic Tissue: A Pilot Study
Mansour A. Alghamdi,
Laith N. AL-Eitan,
Andrew Stevenson,
Nutan Chaudhari,
Nicole Hortin,
Hilary J. Wallace,
Patricia L. Danielsen,
Mitali Manzur,
Fiona M. Wood,
Mark W. Fear
Affiliations
Mansour A. Alghamdi
Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
Laith N. AL-Eitan
Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan
Andrew Stevenson
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley 6009, Australia
Nutan Chaudhari
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley 6009, Australia
Nicole Hortin
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley 6009, Australia
Hilary J. Wallace
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley 6009, Australia
Patricia L. Danielsen
Department of Dermatology and Copenhagen Wound Healing Center, Copenhagen University Hospital, DK-2400 Copenhagen NV, Denmark
Mitali Manzur
Telethon Kids Institute, Perth Children’s Hospital, The University of Western Australia, Nedlands 6009, Australia
Fiona M. Wood
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley 6009, Australia
Mark W. Fear
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley 6009, Australia
Interactions between keratinocytes and fibroblasts in the skin layers are crucial in normal tissue development, wound healing, and scarring. This study has investigated the role of keloid keratinocytes in regulating collagen production by primary fibroblasts in vitro. Keloid cells were obtained from removed patients’ tissue whereas normal skin cells were discarded tissue obtained from elective surgery procedures. Fibroblasts and keratinocytes were isolated, cultured, and a transwell co-culture system were used to investigate the effect of keratinocytes on collagen production using a ‘scar-in-a-jar’ model. Keloid fibroblasts produced significantly more collagen than normal skin fibroblasts in monoculture at the RNA, secreted protein, and stable fibrillar protein level. When keloid keratinocytes were added to normal skin fibroblasts, expression of collagen was significantly upregulated in most samples, but when added to keloid fibroblasts, collagen I production was significantly reduced. Interestingly, keloid keratinocytes appear to decrease collagen production by keloid fibroblasts. This suggests that signaling in both keratinocytes and fibroblasts is disrupted in keloid pathology.
