The Impact of Wnt Signalling Activation on Ear Canal Dermis: Unravelling the Pathogenesis of Keratosis Obturans | Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23 2023

Author(s)

Saba Zafar Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King´s College London, Guy’s Hospital, SE1 9RT; The Women University Multan, Pakistan

Juan Fons The Women University Multan, Pakistan

Abigail S. Tucker Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King´s College London, Guy’s Hospital, SE1 9RT

Abstract

Keratosis obturans is an external auditory canal disease and characterized by the amassing of dense plugs of desquamated keratin within the auditory meatus which results in acute HI and severe pain. We identified a possible mice model for keratosis Obturans which was designed as a mouse model for cancer studies. We aimed to reveal the underlying pathology and development mechanism of keratosis Obturans which in turn would be helpful to understand the pathology of keratosis Obturans in humans. Hyperplasia of the epithelium and alteration in migration of epithelial cells had been reported in Keratosis Obturans pathology. Epidermal differentiation and stratification were achieved by a cross-talk between fibroblast from the dermis and epithelial cells from the epidermis. We focused on Canonical Wntsignalling pathway having an established function in proliferation. To determine the effect of Wntsignalling activation in FSP1 positives fibroblast on the external canal epithelium and its role in the onset of pathogenesis, we used ear tissues from FSP1-cre negative ß-Catflox/floxEx3 wild type and FSP1-cre positive ß-Catflox/floxEx3 mutant gain of function mice to analyze the epithelial phenotype. Histological analysis showed an obstructed ear canal filled with keratin and a hyperproliferative epithelium as seen by PCNA immunostaining, both features resemble Keratosis Obturans. Differences in epidermal stratification and abnormal K14 and K10 marker location suggest that the epithelial differentiation program is altered in these mutant mice. Canonical Wnt signaling activation in ectopic osteocytes was also confirmed via beta-catenin immune-fluorescence assay. This indicates a change of chondrocyte to osteocyte fate of the perichondrium. Nuclear beta-catenin was observed to be localized in the dermal fibroblast but not in epithelial cells, confirming specific cre activity. These results showed that dermal Wnt signaling over activation leads to the hyperproliferative epidermis with Keratin Obturans features. Therefore, we suggest that Keratosis obturans may be due to defects in dermal fibroblast rather than being an epidermis problem.

Publication Details

Page(s) 279-279

DOI DOI not available

Published Journal: Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23, Volume: 0, Issue: 0, Year: 2023

Keywords

Keratosis Obturans Beta Catenin FSP1Cre WNT signalling Hearing loss

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