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Biomed Res Int. 2018 May 16;2018:2847873. doi: 10.1155/2018/2847873. eCollection 2018.

HPV16-E6 Oncoprotein Activates TGF-β and Wnt/β-Catenin Pathways in the Epithelium-Mesenchymal Transition of Cataracts in a Transgenic Mouse Model.

Author information

1
Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México, Mexico.
2
Unit of Health Sciences, Faculty of Odontology, Universidad Autónoma de Baja California, Mexicali, BC, Mexico.
3
Research Unit, Laboratory of Genetics and Molecular Diagnosis, Hospital Juárez de México, Ciudad de México, Mexico.
4
Department of Physiology Biophysics and Neurosciences, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México, Mexico.
5
Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, 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 Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México, Mexico.
9
Department of Cellular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México, Mexico.

Abstract

Objective:

This work aimed to determine if cataractous changes associated with EMT occurring in the K14E6 mice lenses are associated with TGF-β and Wnt/β-catenin signaling activation.

Materials and Methods:

Cataracts of K14E6 mice were analysed histologically; and components of TGF-β and Wnt/β-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. The endogenous stabilisation of Smad7 protein was also assessed using an HDAC inhibitor.

Results:

The 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-β and Wnt/β-catenin pathways, and the accumulation of MTA1 protein. Finally, the stabilisation of Smad7 protein diminishes cell proliferation, as well as MTA1 protein levels.

Conclusion:

The HPV16-E6 oncoprotein induces EMT in transgenic mice cataracts. The molecular mechanism may involve TGF-β and Wnt/β-catenin pathways, suggesting that the K14E6 transgenic mouse could be a useful model for the study or treatment of EMT-induced cataracts.

PMID:
29888254
PMCID:
PMC5977056
DOI:
10.1155/2018/2847873
[Indexed for MEDLINE]
Free PMC Article

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