Endothelial dysfunction and Claudin 5 regulation during acrolein-induced lung injury

An Soo Jang, Vincent J. Concel, Kiflai Bein, Kelly A. Brant, Shannen Liu, Hannah Pope-Varsalona, Richard A. Dopico, Y. P.Peter Di, Daren L Knoell, Aaron Barchowsky, George D. Leikauf

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

An integral membrane protein, Claudin 5 (CLDN5), is a critical component of endothelial tight junctions that control pericellular permeability. Breaching of endothelial barriers is a key event in the development of pulmonary edema during acute lung injury (ALI). A major irritant in smoke, acrolein can induce ALI possibly by altering CLDN5 expression. This study sought to determine the cell signaling mechanism controlling endothelial CLDN5 expression during ALI. To assess susceptibility, 12 mouse strains were exposed to acrolein (10 ppm, 24 h), and survival monitored. Histology, lavage protein, and CLDN5 transcripts were measured in the lung of the most sensitive and resistant strains. CLDN5 transcripts and phosphorylation status of forkhead box O1 (FOXO1) and catenin (cadherin-associated protein) beta 1 (CTNNB1) proteins were determined in control and acrolein-treated human endothelial cells. Mean survival time (MST) varied more than 2-fold among strains with the susceptible (BALB/cByJ) and resistant (129X1/SvJ) strains (MST, 17.3 ± 1.9 h vs. 41.4 ± 5.1 h, respectively). Histological analysis revealed earlier perivascular enlargement in the BALB/cByJ than in 129X1/SvJ mouse lung. Lung CLDN5 transcript and protein increased more in the resistant strain than in the susceptible strain. In human endothelial cells, 30 nM acrolein increased CLDN5 transcripts and increased p-FOXO1 protein levels. The phosphatidylinositol 3-kinase inhibitor LY294002 diminished the acrolein-induced increased CLDN5 transcript. Acrolein (300 nM) decreased CLDN5 transcripts, which were accompanied by increased FOXO1 and CTNNB1. The phosphorylation status of these transcription factors was consistent with the observed CLDN5 alteration. Preservation of endothelial CLDN5 may be a novel clinical approach for ALI therapy.

Original languageEnglish (US)
Pages (from-to)483-490
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume44
Issue number4
DOIs
StatePublished - Apr 1 2011

Fingerprint

Claudin-5
Acrolein
Lung Injury
Acute Lung Injury
Catenins
Phosphorylation
Endothelial cells
Cadherins
Proteins
Lung
Endothelial Cells
Claudins
Phosphatidylinositol 3-Kinase
Cell signaling
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Histology
Tight Junctions
Irritants
Therapeutic Irrigation
Pulmonary Edema

Keywords

  • ARDS
  • Carboxyl stress
  • Perivascular edema
  • Smoke inhalation
  • Vascular permeability

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Jang, A. S., Concel, V. J., Bein, K., Brant, K. A., Liu, S., Pope-Varsalona, H., ... Leikauf, G. D. (2011). Endothelial dysfunction and Claudin 5 regulation during acrolein-induced lung injury. American journal of respiratory cell and molecular biology, 44(4), 483-490. https://doi.org/10.1165/rcmb.2009-0391OC

Endothelial dysfunction and Claudin 5 regulation during acrolein-induced lung injury. / Jang, An Soo; Concel, Vincent J.; Bein, Kiflai; Brant, Kelly A.; Liu, Shannen; Pope-Varsalona, Hannah; Dopico, Richard A.; Di, Y. P.Peter; Knoell, Daren L; Barchowsky, Aaron; Leikauf, George D.

In: American journal of respiratory cell and molecular biology, Vol. 44, No. 4, 01.04.2011, p. 483-490.

Research output: Contribution to journalArticle

Jang, AS, Concel, VJ, Bein, K, Brant, KA, Liu, S, Pope-Varsalona, H, Dopico, RA, Di, YPP, Knoell, DL, Barchowsky, A & Leikauf, GD 2011, 'Endothelial dysfunction and Claudin 5 regulation during acrolein-induced lung injury', American journal of respiratory cell and molecular biology, vol. 44, no. 4, pp. 483-490. https://doi.org/10.1165/rcmb.2009-0391OC
Jang, An Soo ; Concel, Vincent J. ; Bein, Kiflai ; Brant, Kelly A. ; Liu, Shannen ; Pope-Varsalona, Hannah ; Dopico, Richard A. ; Di, Y. P.Peter ; Knoell, Daren L ; Barchowsky, Aaron ; Leikauf, George D. / Endothelial dysfunction and Claudin 5 regulation during acrolein-induced lung injury. In: American journal of respiratory cell and molecular biology. 2011 ; Vol. 44, No. 4. pp. 483-490.
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