Mohammad Ghazizadeh, S Igota, S Egawa and M Tosa
Posters: Surgery Curr Res
Wingless type (Wnt) signaling pathways play key roles in various cellular functions including proliferation, differentiation, survival, apoptosis and migration. We studied the role of Wnt signaling pathway in keloid pathogenesis. Primary fibroblast cultures and tissue samples from keloid (KF) and normal appearing dermis (NF) were used. The expression and function of Wnt5a, frizzled4 receptor, ROR2 and the Wnt signaling downstream targets, GSK3-beta and beta-catenin were assessed using semi-quantitative RT-PCR, Western blot, or immunohistochemical methods. We found a higher expression of beta-catenin in KF compared to NF. No detectable levels of FZD4 receptor and ROR2 proteins were observed in both NF and KF. Functional analysis showed that treatment of NF and KF with recombinant Wnt5a peptide resulted in an increase in protein levels of total beta-catenin and phosphorylated beta-catenin at Ser33/37/Thr41 but no significant change in phosphorylated beta-catenin at Ser45/Thr41 positions. In addition, the expression of total GSK3-betaprotein was not affected, but its phosphorylated/inactivated form was increased in NF and KF. Inhibition of Wnt5a by specific anti-Wnt5a antibody reversed these effects. Taken together, these findings highlight a potential role for a Wnt/beta-catenin pathway triggered by Wnt5a in keloid pathogenisis. Wnt5a/beta-catenin signaling pathway may provide a new molecular target for developing therapeutic strategies for keloid.
Mohammad Ghazizadeh has completed his MD in 1975 and Residency in Urologic surgery in 1980. In 1984, he has received his Doctor of Medical Sciences from the University of Tokushima School of Medicine, Japan. He is an Associate Professor and Chief at the Department of Molecular Pathology, Institute of Gerontology and Nippon Medical School, Japan. He has served as the Director of the Central Institute for Electron Microscopy Research at Nippon Medical School, Tokyo, Japan. He has published more than 100 papers in reputed journals. He is Editor-in-Chief of the American Journal of Experimental and Clinical Research andhasalso served as an Editorial Board Member of the Journal of Nippon Medical School, The Open Dermatology Journal, World Journal of Dermatology, and formerly Journal of Submicroscopic Cytology and Cytopathology.
