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

Menglin Liu, Lianghui Zhang, Glenn Marsboom, Ankit Jambusaria, Shiqin Xiong, Peter T. Toth, Elizaveta V. Benevolenskaya, Jalees Rehman () and Asrar B. Malik ()
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Menglin Liu: The University of Illinois College of Medicine
Lianghui Zhang: The University of Illinois College of Medicine
Glenn Marsboom: The University of Illinois College of Medicine
Ankit Jambusaria: The University of Illinois College of Medicine
Shiqin Xiong: The University of Illinois College of Medicine
Peter T. Toth: The University of Illinois College of Medicine
Elizaveta V. Benevolenskaya: The University of Illinois College of Medicine
Jalees Rehman: The University of Illinois College of Medicine
Asrar B. Malik: The University of Illinois College of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-10134-y

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