Title

Protein kinase D promotes airway epithelial barrier dysfunction and permeability through down-regulation of claudin-1

Authors

Huachen Gan, The University of Texas Health Science Center at Tyler
Guibo Wang, The University of Texas Health Science Center at Tyler
Qin Hao, The University of Texas Health Science Center at TylerFollow
Q. Jane Wang
Hua Tang, University of Texas Health Science Center at Tyler

Document Type

Article

Publication Date

Spring 1-4-2021

Abstract

At the interface between host and external environment, the airway epithelium serves as a major protective barrier. In the present study we show that protein kinase D (PKD) plays an important role in the formation and integrity of the airway epithelial barrier. Either inhibition of PKD activity or silencing of PKD increased transepithelial electrical resistance (TEER), resulting in a tighter epithelial barrier. Among the three PKD isoforms, PKD3 knockdown was the most efficient one to increase TEER in polarized airway epithelial monolayers. In contrast, overexpression of PKD3 wild type, but not PKD3 kinase-inactive mutant, disrupted the formation of apical intercellular junctions and their reassembly, impaired the development of TEER, and increased paracellular permeability to sodium fluorescein in airway epithelial monolayers. We further found that overexpression of PKD, in particular PKD3, markedly suppressed the mRNA and protein levels of claudin-1 but had only minor effects on the expression of other tight junctional proteins (claudin-3, claudin-4, claudin-5, occludin, and ZO-1) and adherent junctional proteins (E-cadherin and β-catenin). Immunofluorescence study revealed that claudin-1 level was markedly reduced and almost disappeared from intercellular contacts in PKD3-overexpressed epithelial monolayers and that claudin-4 was also restricted from intercellular contacts and tended to accumulate in the cell cytosolic compartments. Last, we found that claudin-1 knockdown prevented TEER elevation by PKD inhibition or silencing in airway epithelial monolayers. These novel findings indicate that PKD negatively regulates human airway epithelial barrier formation and integrity through down-regulation of claudin-1, which is a key component of tight junctions.

Description

© 2013 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.

Persistent Identifier

http://hdl.handle.net/10950/4392

Publisher

Elsevier / American Society for Biochemistry and Molecular Biology

Permanent Email Address

htang@uttyler.edu

Recommended Citation

Gan, Huachen; Wang, Guibo; Hao, Qin; Wang, Q. Jane; and Tang, Hua, "Protein kinase D promotes airway epithelial barrier dysfunction and permeability through down-regulation of claudin-1" (2021). Cellular and Molecular Biology Faculty Publications and Presentations. Paper 13.