caa a22 4500 606234780 CHVBK 20210128101239.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2526-8 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2526-8 Methotrexate modulates the expression of MMP-1 and type 1 collagen in dermal fibroblast [Elektronische Daten] [Layla Nabai, Ruhangiz Kilani, Farzian Aminuddin, Yunyuan Li, Aziz Ghahary] Methotrexate (MTX), an anti-metabolite and anti-inflammatory drug, has been used to effectively manage and prevent keloids, but its mechanism(s) of action has not been elucidated. Our study sought to evaluate the effect of MTX on the production of key extra cellular matrix components, collagen, and matrix metalloproteinase-1 (MMP-1), produced by fibroblasts and involved in development of fibrosis. The proliferation and viability of cultured human dermal fibroblasts in response to different concentrations of MTX were determined using cell counting and MTT assay, respectively. Western blot analysis was used to determine the levels of both intracellular and secreted type 1 collagen and MMP-1. The results showed no significant changes in the proliferation of fibroblasts treated with 50ng/ml of MTX as compared to that of control. Under the same experimental conditions, the level of secreted and intracellular type I collagen was markedly reduced and, conversely, the level of MMP-1 increased in treated neonatal, adult, and hypertrophic scar fibroblasts as compared with those of controls. The possible involvement of MTX-induced extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in MMP-1 production was also studied and the result showed an increase in phosphorylated ERK 1/2 in response to MTX treatment. In summary, the findings of this study revealed that MTX significantly reduced collagen production in different strains of fibroblasts derived from neonatal, adult, and hypertrophic scar tissues, while under the same experimental conditions, it increased the expression of MMP-1. As such, our findings validate and identify a potential mechanism through which MTX functions as an anti-fibrogenic factor in treating fibroproliferative disorders. Springer Science+Business Media New York, 2015 Fibrosis nationallicence Methotrexate nationallicence Collagen nationallicence Matrix metalloproteinase nationallicence Nabai Layla BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut Kilani Ruhangiz BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut Aminuddin Farzian BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut Li Yunyuan BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut Ghahary Aziz BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 213-224 0300-8177 409:1-2<213 2015 409 11010 https://doi.org/10.1007/s11010-015-2526-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2526-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nabai Layla BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut NATIONALLICENCE 700 1- Kilani Ruhangiz BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut NATIONALLICENCE 700 1- Aminuddin Farzian BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut NATIONALLICENCE 700 1- Li Yunyuan BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut NATIONALLICENCE 700 1- Ghahary Aziz BC Professional Firefighters' Burn and Wound Healing Research Laboratory, Department of Surgery/Plastic Surgery, University of British Columbia, Vancouver, Canada aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 213-224 0300-8177 409:1-2<213 2015 409 11010