title: Vitiligo patient-derived keratinocytes exhibit characteristics of normal wound healing via epithelial to mesenchymal transition.
abstract: Vitiligo is an autoimmune disorder that leads to depigmentation of skin via melanocyte dysfunction. Keratinocyte-induced toxicity is one among the several etiological factors implicated for vitiligo, and hence, autologous keratinocyte grafting is projected as one of the primary mode of treatment for vitiligo. However, reports indicate that perilesional keratinocytes not only display signatures of apoptosis but also could secrete cytokines and mediators which have antagonistic effect on proliferation or survival. Therefore, we investigated how vitiligo patients' derived keratinocytes respond to surplus amounts of inflammatory cytokines and whether they recapitulate events that take place during conventional wound healing. The primary objective of our study was to determine whether keratinocytes isolated from a vitiligo patient would undergo epithelial-mesenchymal transition similar to their normal counterparts upon induction with inflammatory cytokines such as TGF-b1 and EGF. We found that these keratinocytes undergo EMT during wound repair accompanied with increase in the levels of mesenchymal markers and ECM proteins; decrease in the levels of epithelial markers and enhanced migratory ability. Besides, we also demonstrated that EMT induction leads to activation of SMAD and MAPK pathways via Ras, Raf, PAI 1, Snail, Slug and ZO1. To our knowledge, this is the first report on the characterization of primary keratinocytes isolated from vitiligo patients with respect to their wound healing capacity.
authors.affiliation: School of Regenerative Medicine, Manipal University, Yelahanka, Bangalore, India.
authors.forename: Poulomi
authors.initials: P
authors.lastname: Banerjee
authors.forename: Sandhyaa
authors.initials: S
authors.lastname: Venkatachalam
authors.forename: Murali Krishna
authors.initials: MK
authors.lastname: Mamidi
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bhonde
authors.forename: Krupa
authors.initials: K
authors.lastname: Shankar
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Pal
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000473:pathology* / Q000502:physiology; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D051785:Smad Proteins / Q000378:metabolism; D014820:Vitiligo / Q000473:pathology* / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology
chemical_list: D016207:Cytokines; D051785:Smad Proteins
keywords: Epithelial to mesenchymal transition; cytokines and wound healing; keratinocytes; migration; vitiligo