Hlutverk umritunarþáttarins p63 í þekju efri loftvega - verkefni lokið
Fréttatilkynning verkefnisstjóra
Bronchial epithelial differentiation and epithelial repair are critical in the pathogenesis of several lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis and lung cancer. Therefore, it is important to understand the molecular events regulating the hierarchical differentiation steps and repair mechanisms in airway epithelia.
One of the key transcriptional regulators in various epithelial tissues is p63, a member of the p53 family of transcription factors. p63 exhibits a restricted expression pattern with high levels being expressed in certain basal epithelial cells of diverse organs such as the skin, breast and prostate. Furthermore, p63 has been shown to be a master regulator of the epithelial differentiation program, especially involved in the regulation of stratified epithelium such as the skin. In this project we have used VA-10, a bronchial cell line developed in our laboratory to study the role of p63 in the lung epithelium, specifically during formation and maintenance of a pseudostratified epithelium. We demonstrated that ΔNp63 is the major isoform in the human lung. p63 was shown to be critical for cell proliferation and migration and also shown to be involved in preventing cellular senescence. Importantly, generation of pseudostratified epithelium was dependent on p63 expression. We conclude that these results strongly implicate p63 in the formation and maintenance of differentiated pseudostratified bronchial epithelium. Furthermore, in idiopathic pulmonary fibrosis (IPF), we showed that p63 positive basal cells showed a markedly abnormal phenotype and in vitro, basal cells were shown to be able to undergo epthelial-to-mesenchymal transition, mimicking the phenotype seen in IPF patients.
Application
of results
This project has increased the strength of our
research group and facilitated both national and international
collaboration. The project allowed us to
train young scientists, and two students graduated, one with a masters degree
and another with a PhD degree. We will continue to work on p63 and its role in
regulating the airway epithelium. We
believe that our airway models are important and useful for unraveling new
pathways in lung diseases, such as idiopathic pulmonary fibrosis and lung
cancer.
Heiti
verkefnis: Hlutverk umritunarþáttarins p63 í þekju efri loftvega
Verkefnisstjóri: Magnús Karl Magnússon, Háskóla Íslands
Tegund styrks:
Verkefnisstyrkur
Styrktímabil: 2012-2014
Fjárhæð styrks: 18,46
millj. kr. alls
Tilvísunarnúmer
Rannís: 120423
