Research Article
HPV16-E6 Oncoprotein Activates TGF-
and Wnt/-Catenin Pathways in the Epithelium-Mesenchymal
Transition of Cataracts in a Transgenic Mouse Model
Genaro Rodríguez-Uribe ,
1
Nicolas Serafín-Higuera ,
2
Gabriela Damian-Morales,
3
Enoc Mariano Cortés-Malagón,
3
Vicky García-Hernández,
4
Odette Verdejo-Torres,
4
Jessica Paulina Campos-Blázquez,
4
Cynthia R. Trejo-Muñoz,
5
Rubén Gerardo Contreras ,
4
Rodolfo Ocadiz-Delgado ,
1
Carmen Palacios-Reyes,
3
Paul F. Lambert,
6
Anne E. Griep,
7
Teresa Mancilla-Percino,
8
Jaime Escobar-Herrera,
9
Elizabeth Álvarez-Ríos,
1
Carlos Ugarte-Briones,
3
José Moreno,
3
Patricio Gariglio ,
1
and José Bonilla-Delgado
3
1
Department of Genetics and Molecular Biology, Centro de Investigaci´ on y de Estudios Avanzados del Instituto Polit´ ecnico Nacional
(CINVESTAV-IPN), Ciudad de M´ exico, Mexico
2
Unit of Health Sciences, Faculty of Odontology, Universidad Aut´ onoma de Baja California, Mexicali, BC, Mexico
3
Research Unit, Laboratory of Genetics and Molecular Diagnosis, Hospital Ju´ arez de M´ exico, Ciudad de M´ exico, Mexico
4
Department of Physiology Biophysics and Neurosciences, Centro de Investigaci´ on y de Estudios Avanzados del Instituto Polit´ ecnico
Nacional (CINVESTAV-IPN), Ciudad de M´ exico, Mexico
5
Escuela Superior de Medicina, Instituto Polit´ ecnico Nacional, Ciudad de M´ exico, Mexico
6
McArdle Laboratory for Cancer Research, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin, USA
7
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
8
Department of Chemistry, Centro de Investigaci´ on y de Estudios Avanzados del Instituto Polit´ ecnico Nacional (CINVESTAV-IPN),
Ciudad de M´ exico, Mexico
9
Department of Cellular Biology, Centro de Investigaci´ on y de Estudios Avanzados del Instituto Polit´ ecnico Nacional (CINVESTAV-
IPN), Ciudad de M´ exico, Mexico
Correspondence should be addressed to Patricio Gariglio; vidal@cinvestav.mx and Jos´ e Bonilla-Delgado; jbonilla@cinvestav.mx
Received 30 November 2017; Revised 14 March 2018; Accepted 3 April 2018; Published 16 May 2018
Academic Editor: Bo Zuo
Copyright © 2018 Genaro Rodr´ıguez-Uribe et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. is work aimed to determine if cataractous changes associated with EMT occurring in the K14E6 mice lenses are
associated with TGF- and Wnt/-catenin signaling activation. Materials and Methods. Cataracts of K14E6 mice were analysed
histologically; and components of TGF- and Wnt/-catenin signaling were evaluated by Western blot, RT-qPCR, in situ RT-PCR,
IHC, or IF technics. Metalloproteinases involved in EMT were also assayed using zymography. e endogenous stabilisation of
Smad7 protein was also assessed using an HDAC inhibitor. Results. e K14E6 mice, which displayed binocular cataracts in 100%
of the animals, exhibited loss of tissue organisation, cortical liquefaction, and an increase in the number of hyperproliferative-
nucleated cells with mesenchymal-like characteristics in the lenses. Changes in lenses’ cell morphology were due to actin filaments
reorganisation, activation of TGF- and Wnt/-catenin pathways, and the accumulation of MTA1 protein. Finally, the stabilisation
of Smad7 protein diminishes cell proliferation, as well as MTA1 protein levels. Conclusion. e HPV16-E6 oncoprotein induces
EMT in transgenic mice cataracts. e molecular mechanism may involve TGF- and Wnt/-catenin pathways, suggesting that
the K14E6 transgenic mouse could be a useful model for the study or treatment of EMT-induced cataracts.
Hindawi
BioMed Research International
Volume 2018, Article ID 2847873, 17 pages
https://doi.org/10.1155/2018/2847873