Tight junction protein claudin-4 is modulated via ΔNp63 in human keratinocytes.

Abstract

In the epidermis, tight junction (TJ) structure is specifically located in the stratum granulosum, where the expression of ΔNp63, a p53 family transcription factor, is attenuated. Since the relationship between ΔNp63 and barrier function has not been fully uncovered, we assessed expression profiles of TJ proteins in skin tissues and cultured keratinocytes. The results showed that expression of ΔNp63 and that of claudin-4 were inversely correlated in healthy human epidermis. In vitro studies using HaCaT keratinocytes revealed functional relevance of ΔNp63 and claudin-4. Curiously, Toll-like receptor (TLR)-3 ligand, which is known to be liberated from damaged cells, suppressed ΔNp63 expression and concomitantly upregulated claudin-4 expression in primary keratinocytes. More interestingly, a broad expression pattern of claudin-4 was found in the epidermis of atopic dermatitis (AD), a barrier defect disorder, which contains ΔNp63-lacking keratinocytes as we reported previously. Therefore, upregulation of claudin-4 expression regulated by ΔNp63 might be associated with complementary or repair responses of damaged keratinocytes with AD.

• Authors: Terufumi Kubo, Kotaro Sugimoto, Takashi Kojima, Norimasa Sawada, Noriyuki Sato, Shingo Ichimiya
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 455 Issue 3-4 Pg. 205-11 (Dec 12 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 25449274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• CLDN4 protein, human
• Claudin-4
• Ligands
• RNA, Small Interfering
• TLR3 protein, human
• TP63 protein, human
• Toll-Like Receptor 3
• Transcription Factors
• Tumor Suppressor Proteins

Topics

• Biopsy
• Cell Differentiation
• Claudin-4 (metabolism)
• Dermatitis, Atopic (metabolism)
• Epidermis (metabolism)
• Gene Expression Regulation
• Humans
• Keratinocytes (cytology, metabolism)
• Ligands
• RNA, Small Interfering (metabolism)
• Real-Time Polymerase Chain Reaction
• Skin (metabolism)
• Tight Junctions (metabolism)
• Toll-Like Receptor 3 (metabolism)
• Transcription Factors (metabolism)
• Tumor Suppressor Proteins (metabolism)