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TOPICAL SUBSTITUTION OF TRANSGLUTAMINASE 1 FOR THE TREATMENT OF CONGENITAL ICHTHYOSIS

Barragan, Inmaculada (2019) TOPICAL SUBSTITUTION OF TRANSGLUTAMINASE 1 FOR THE TREATMENT OF CONGENITAL ICHTHYOSIS. Masters thesis, University of Huddersfield.

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Abstract

Autosomal recessive congenital ichthyosis (ARCI) is a rare cornification disorder with impaired skin barrier function and with no causative treatment available. Eleven genes are involved in different ARCI phenotypes, all related to epidermal differentiation. Mutation inTGM1 is the main cause of ARCI, and it encodes for the enzyme transglutaminase 1 (TGase1), which is involved in the keratinocyte differentiation and in the formation of the cornified cell envelope. Mutations in TGM1 cause lamellar ichthyosis and congenital ichthyosiform erythroderma phenotypes, causing also self-healing collodion babies.

In this project, we aimed to study the fate of the protein-loaded thermoresponsive PNIPAM-dPG nanogel for cutaneous protein TGase1 delivery for restoring the skin barrier function in ARCI patients with TGM1 mutation.

To accomplish this, TGase1 delivery was analysed in keratinocytes grown in a 2D monolayer and in 3D skin models. We first studied the gene expression of TGM1 and other specific markers for ARCI on RNA level. As TGM1 was expressed in all our cell models (human control, human ARCI-patient with TGM1 mutation, and pig control keratinocytes), we subsequently developed three-dimensional skin models to evaluate the destiny of the TGase1/NG complex in the skin. Observing the successful delivery of TGase1 and nanogel in the epidermis, we carried out the study of their location in keratinocytesina 2D monolayer. Our findings suggested that TGase1 and nanogel enter the keratinocytes, release one from each other, and they are located around the nuclei, in thecytoplasm and in the plasma membrane.

Item Type: Thesis (Masters)
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology
Schools: School of Applied Sciences
Depositing User: Rebecca Hill
Date Deposited: 18 Jul 2019 13:25
Last Modified: 18 Jul 2019 13:30
URI: http://eprints.hud.ac.uk/id/eprint/34946

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