Sox17 is required for endothelial regeneration following inflammation-induced vascular injury.

Nat Commun 2019 05 9;10(1):2126. Epub 2019 May 9.

Department of Pharmacology, The University of Illinois College of Medicine, Chicago, IL, 60612, USA.

Repair of the endothelial cell barrier after inflammatory injury is essential for tissue fluid homeostasis and normalizing leukocyte transmigration. However, the mechanisms of endothelial regeneration remain poorly understood. Here we show that the endothelial and hematopoietic developmental transcription factor Sox17 promotes endothelial regeneration in the endotoxemia model of endothelial injury. Genetic lineage tracing studies demonstrate that the native endothelium itself serves as the primary source of endothelial cells repopulating the vessel wall following injury. We identify Sox17 as a key regulator of endothelial cell regeneration using endothelial-specific deletion and overexpression of Sox17. Endotoxemia upregulates Hypoxia inducible factor 1α, which in turn transcriptionally activates Sox17 expression. We observe that Sox17 increases endothelial cell proliferation via upregulation of Cyclin E1. Furthermore, endothelial-specific upregulation of Sox17 in vivo enhances lung endothelial regeneration. We conclude that endotoxemia adaptively activates Sox17 expression to mediate Cyclin E1-dependent endothelial cell regeneration and restore vascular homeostasis.

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http://dx.doi.org/10.1038/s41467-019-10134-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509327PMC
May 2019
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References

(Supplied by CrossRef)

P Rajendran et al.
Int. J. Biol. Sci. 2013

Y Komarova et al.
Annu Rev. Physiol. 2010

JE Deanfield et al.
Circulation 2007

PM Vanhoutte et al.
Cardiovasc. Drugs Ther. 2010

YY Zhao et al.
J. Clin. Invest 2006

BT Thompson et al.
N. Engl. J. Med. 2017

MA Matthay et al.
J. Clin. Invest. 2012

MA Matthay et al.
Chest 2010

M Gu et al.
Circ. Res. 2012

JW Lee et al.
Proc. Natl Acad. Sci. USA 2009

GF Curley et al.
Curr. Opin. Crit. Care 2015

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