title: Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients.
abstract: Vitiligo affects 1% of the worldwide population. Halting disease progression and repigmenting the lesional skin represent the two faces of therapeutic challenge in vitiligo. We performed transcriptome analysis on lesional, perilesional, and non-depigmented skin from vitiligo patients and on matched skin from healthy subjects. We found a significant increase in CXCL10 in non-depigmented and perilesional vitiligo skin compared with levels in healthy control skin; however, neither CXCL10 nor other immune factors were deregulated in depigmented vitiligo skin. Interestingly, the WNT pathway, which is involved in melanocyte differentiation, was altered specifically in vitiligo skin. We demonstrated that oxidative stress decreases WNT expression/activation in keratinocytes and melanocytes. We developed an ex vivo skin model and confirmed the decrease activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated ex vivo depigmented skin from vitiligo patients and successfully induced differentiation of resident stem cells into pre-melanocytes. Our results shed light on the previously unrecognized role of decreased WNT activation in the prevention of melanocyte differentiation in depigmented vitiligo skin. Furthermore, these results support further clinical exploration of WNT agonists to repigment vitiligo lesions.
authors: C3M, INSERM U1065, team 12, Nice, France.
authors: Claire
authors: C
authors: Regazzetti
authors: Galderma R&D, Sophia-Antipolis, France.
authors: Florence
authors: F
authors: Joly
authors: Galderma R&D, Sophia-Antipolis, France.
authors: Carine
authors: C
authors: Marty
authors: Galderma R&D, Sophia-Antipolis, France.
authors: Michel
authors: M
authors: Rivier
authors: Galderma R&D, Sophia-Antipolis, France.
authors: Bruno
authors: B
authors: Mehul
authors: Galderma R&D, Sophia-Antipolis, France.
authors: Pascale
authors: P
authors: Reiniche
authors: Galderma R&D, Sophia-Antipolis, France.
authors: Carine
authors: C
authors: Mounier
authors: Galderma R&D, Sophia-Antipolis, France.
authors: Yves
authors: Y
authors: Rival
authors: Galderma R&D, Sophia-Antipolis, France.
authors: David
authors: D
authors: Piwnica
authors: Department of Dermatology, University Hospital Center of Nice, Nice, France.
authors: Marine
authors: M
authors: Cavalié
authors: Department of Plastic Surgery, University Hospital Center of Nice, Nice, France.
authors: Bérengère
authors: B
authors: Chignon-Sicard
authors: C3M, INSERM U1065, team 1, Nice, France.
authors: Robert
authors: R
authors: Ballotti
authors: Galderma R&D, Sophia-Antipolis, France.
authors: Johannes
authors: J
authors: Voegel
authors: C3M, INSERM U1065, team 12, Nice, France; Department of Dermatology, University Hospital Center of Nice, Nice, France. Electronic address: passeron@unice.fr.
authors: Thierry
authors: T
authors: Passeron
mesh_terms: D054357:Chemokine CXCL10 / Q000032:analysis; D020869:Gene Expression Profiling; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000502:physiology; D018384:Oxidative Stress; D012867:Skin / Q000378:metabolism*; D012880:Skin Pigmentation; D014820:Vitiligo / Q000209:etiology / Q000503:physiopathology*; D060449:Wnt Signaling Pathway
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1