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Int. J. Mol. Sci. 2014, 15(4), 5472-5495; doi:10.3390/ijms15045472

Effect of Wnt3a on Keratinocytes Utilizing in Vitro and Bioinformatics Analysis

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Korea
Department of Bio-Informatics, School of Computer and Information Sciences, Galgotias University, Greater Noida 201308, Uttar Pradesh, India
Department of Dermatology, School of Medicine, Kangwon National University Hospital, Chuncheon 200722, Korea
Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India
Department of Pharmacology, College of Medicine, Hallym University, Chuncheon 200704, Korea
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 22 December 2013 / Revised: 7 March 2014 / Accepted: 12 March 2014 / Published: 28 March 2014
(This article belongs to the Collection Advances in Proteomic Research)


Wingless-type (Wnt) signaling proteins participate in various cell developmental processes. A suppressive role of Wnt5a on keratinocyte growth has already been observed. However, the role of other Wnt proteins in proliferation and differentiation of keratinocytes remains unknown. Here, we investigated the effects of the Wnt ligand, Wnt3a, on proliferation and differentiation of keratinocytes. Keratinocytes from normal human skin were cultured and treated with recombinant Wnt3a alone or in combination with the inflammatory cytokine, tumor necrosis factor α (TNFα). Furthermore, using bioinformatics, we analyzed the biochemical parameters, molecular evolution, and protein–protein interaction network for the Wnt family. Application of recombinant Wnt3a showed an anti-proliferative effect on keratinocytes in a dose-dependent manner. After treatment with TNFα, Wnt3a still demonstrated an anti-proliferative effect on human keratinocytes. Exogenous treatment of Wnt3a was unable to alter mRNA expression of differentiation markers of keratinocytes, whereas an altered expression was observed in TNFα-stimulated keratinocytes. In silico phylogenetic, biochemical, and protein–protein interaction analysis showed several close relationships among the family members of the Wnt family. Moreover, a close phylogenetic and biochemical similarity was observed between Wnt3a and Wnt5a. Finally, we proposed a hypothetical mechanism to illustrate how the Wnt3a protein may inhibit the process of proliferation in keratinocytes, which would be useful for future researchers.
Keywords: keratinocyte; tumor necrosis factor; Wnt signaling keratinocyte; tumor necrosis factor; Wnt signaling
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Nam, J.-S.; Chakraborty, C.; Sharma, A.R.; Her, Y.; Bae, K.-J.; Sharma, G.; Doss, G.P.; Lee, S.-S.; Hong, M.-S.; Song, D.-K. Effect of Wnt3a on Keratinocytes Utilizing in Vitro and Bioinformatics Analysis. Int. J. Mol. Sci. 2014, 15, 5472-5495.

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