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

Abstract

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.

• Authors: Yakuto Kaneko, Takayuki Kohno, Takuya Kakuki, Ken-Ichi Takano, Noriko Ogasawara, Ryo Miyata, Shin Kikuchi, Takumi Konno, Tsuyoshi Ohkuni, Ryoto Yajima, Akito Kakiuchi, Shin-Ichi Yokota, Tetsuo Himi, Takashi Kojima
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 10935 (09 07 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28883651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Herpes Simplex Virus Protein Vmw65
• TP63 protein, human
• Transcription Factors
• Trim33 protein, mouse
• Tumor Suppressor Proteins

Topics

• Cells, Cultured
• Cilia (physiology)
• Epithelial Cells (physiology)
• Gene Expression Regulation
• Gene Regulatory Networks
• Herpes Simplex Virus Protein Vmw65
• Humans
• Nasal Mucosa (physiology)
• Organelle Biogenesis
• Respiratory Syncytial Virus Infections
• Respiratory Syncytial Viruses
• Transcription Factors (metabolism)
• Tumor Suppressor Proteins (metabolism)