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Sox17 Mediated Regeneration of the Lung Endothelium Following Acute Lung Injury

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posted on 06.08.2019, 00:00 by Menglin Liu
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 I 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. I 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. I observe that Sox17 increases endothelial cell proliferation via upregulation of Cyclin E1. Furthermore, endothelial-specific upregulation of Sox17 in vivo enhances lung endothelial regeneration. I conclude that endotoxemia adaptively activates Sox17 expression to mediate Cyclin E1-dependent endothelial cell regeneration and restore vascular homeostasis.

History

Advisor

Malik, Asrar B

Chair

Malik, Asrar B

Department

Pharmacology

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Committee Member

Rehman, Jalees Komarova, Yulia Liu, Yuru Khetani, Salman

Submitted date

May 2019

Issue date

13/05/2019

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