The role of transcriptional factor p63 in regulation of epithelial barrier and ciliogenesis of human nasal epithelial cells

Autor: Shin-ichi Yokota, Takayuki Kohno, Ryoto Yajima, Tsuyoshi Ohkuni, Noriko Ogasawara, Takuya Kakuki, Kenichi Takano, Takumi Konno, Ryo Miyata, Tetsuo Himi, Takashi Kojima, Shin Kikuchi, Akito Kakiuchi, Yakuto Kaneko
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-017-11481-w
Popis: Disruption of nasal epithelial tight junctions (TJs) and ciliary dysfunction are found in patients with chronic rhinosinusitis (CRS) and nasal polyps (NPs), along with an increase of p63-positive basal cells and histone deacetylase (HDAC) activity. To investigate these mechanisms, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were transfected with siRNAs of TAp63 and ΔNp63, treated with the NF-kB inhibitor curucumin and inhibitors of HDACs, and infected with respiratory syncytial virus (RSV). In TERT-HNECs, knockdown of p63 by siRNAs of TAp63 and ΔNp63, induced claudin-1 and -4 with Sp1 activity and enhanced barrier and fence functions. The knockdown of p63 enhanced the number of microvilli with the presence of cilia-like structures. Treatment with curcumin and inhibitors of HDACs, or infection with RSV prevented expression of p63 with an increase of claudin-4 and the number of microvilli. The knockdown or downregulation of p63 inhibited phospho-p38MAPK, and the p38MAPK inhibitor downregulated p63 and upregulated the barrier function. Thus, epithelial barrier and ciliogenesis of nasal epithelium are regulated in a p63-negative manner in normal and upper airway diseases. Understanding of the regulation of p63/p38 MAPK/NF-κB may be important in the therapy for airway allergy and its drug delivery system.
Databáze: OpenAIRE
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