Sox18 Preserves the Pulmonary Endothelial Barrier Under Conditions of Increased Shear Stress

Christine M. Gross, Saurabh Aggarwal, Sanjiv Kumar, Jing Tian, Anita Kasa, Natalia Bogatcheva, Sanjeev A. Datar, Alexander D. Verin, Jeffrey R. Fineman, Stephen M. Black

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Shear stress secondary to increased pulmonary blood flow (PBF) is elevated in some children born with congenital cardiac abnormalities. However, the majority of these patients do not develop pulmonary edema, despite high levels of permeability inducing factors. Previous studies have suggested that laminar fluid shear stress can enhance pulmonary vascular barrier integrity. However, little is known about the mechanisms by which this occurs. Using microarray analysis, we have previously shown that Sox18, a transcription factor involved in blood vessel development and endothelial barrier integrity, is up-regulated in an ovine model of congenital heart disease with increased PBF (shunt). By subjecting ovine pulmonary arterial endothelial cells (PAEC) to laminar flow (20dyn/cm2), we identified an increase in trans-endothelial resistance (TER) across the PAEC monolayer that correlated with an increase in Sox18 expression. Further, the TER was also enhanced when Sox18 was over-expressed and attenuated when Sox18 expression was reduced, suggesting that Sox18 maintains the endothelial barrier integrity in response to shear stress. Further, we found that shear stress up-regulates the cellular tight junction protein, Claudin-5, in a Sox18 dependent manner, and Claudin-5 depletion abolished the Sox18 mediated increase in TER in response to shear stress. Finally, utilizing peripheral lung tissue of 4 week old shunt lambs with increased PBF, we found that both Sox18 and Claudin-5 mRNA and protein levels were elevated. In conclusion, these novel findings suggest that increased laminar flow protects endothelial barrier function via Sox18 dependent up-regulation of Claudin-5 expression. J. Cell. Physiol. 229: 1802-1816, 2014.

Original languageEnglish (US)
Pages (from-to)1802-1816
Number of pages15
JournalJournal of Cellular Physiology
Volume229
Issue number11
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Claudin-5
Shear stress
Lung
Blood
Endothelial cells
Laminar flow
Tight Junction Proteins
Blood Vessels
Sheep
Up-Regulation
Endothelial Cells
Blood vessels
Claudins
Microarrays
Monolayers
Transcription Factors
Pulmonary Edema
Microarray Analysis
Tissue
Messenger RNA

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Sox18 Preserves the Pulmonary Endothelial Barrier Under Conditions of Increased Shear Stress. / Gross, Christine M.; Aggarwal, Saurabh; Kumar, Sanjiv; Tian, Jing; Kasa, Anita; Bogatcheva, Natalia; Datar, Sanjeev A.; Verin, Alexander D.; Fineman, Jeffrey R.; Black, Stephen M.

In: Journal of Cellular Physiology, Vol. 229, No. 11, 2014, p. 1802-1816.

Research output: Contribution to journalArticle

Gross, CM, Aggarwal, S, Kumar, S, Tian, J, Kasa, A, Bogatcheva, N, Datar, SA, Verin, AD, Fineman, JR & Black, SM 2014, 'Sox18 Preserves the Pulmonary Endothelial Barrier Under Conditions of Increased Shear Stress', Journal of Cellular Physiology, vol. 229, no. 11, pp. 1802-1816. https://doi.org/10.1002/jcp.24633
Gross, Christine M. ; Aggarwal, Saurabh ; Kumar, Sanjiv ; Tian, Jing ; Kasa, Anita ; Bogatcheva, Natalia ; Datar, Sanjeev A. ; Verin, Alexander D. ; Fineman, Jeffrey R. ; Black, Stephen M. / Sox18 Preserves the Pulmonary Endothelial Barrier Under Conditions of Increased Shear Stress. In: Journal of Cellular Physiology. 2014 ; Vol. 229, No. 11. pp. 1802-1816.
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