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Updated: Dec 26, 2025

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
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mtDNA Activates cGAS Signaling and Suppresses the YAP-Mediated Endothelial Cell Proliferation Program to Promote

Long Shuang Huang1, Zhigang Hong1, Wei Wu2

  • 1Department of Pharmacology and the Center for Lung and Vascular Biology, The University of Illinois College of Medicine, Chicago, IL 60612, USA.

Immunity
|March 14, 2020
PubMed

Insights

Bacterial endotoxin LPS triggers mitochondrial DNA release, activating cGAS-YAP signaling and hindering endothelial cell repair. Restoring this pathway may improve healing after inflammatory injury.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Cytosolic DNA is a danger signal, but its release and role in tissue injury are unclear.
  • Endothelial cells are crucial for tissue repair and function.

Purpose of the Study:

  • To elucidate the mechanism of self-DNA release into the cytosol.
  • To investigate the role of this process in inflammatory tissue injury and endothelial cell regeneration.

Main Methods:

  • Investigated lipopolysaccharide (LPS)-induced mitochondrial DNA (mtDNA) release in endothelial cells.
  • Assessed the role of Gasdermin D, cGAS, and YAP1 signaling in mtDNA-mediated responses.
  • Utilized a mouse model of inflammatory lung injury to evaluate endothelial regeneration.

Main Results:

  • Internalized LPS activated Gasdermin D, causing mitochondrial pores and cytosolic mtDNA release.
  • Released mtDNA was sensed by cGAS, producing cGAMP that suppressed endothelial cell proliferation via YAP1.
  • Endothelial cells in inflammatory injury sites showed impaired regeneration.
  • Deletion of cGas in mice restored endothelial regeneration in lung injury models.

Conclusions:

  • Endothelial Gasdermin D-activated cGAS-YAP signaling impairs endothelial regenerative capacity after inflammatory injury.
  • Targeting this pathway presents a potential therapeutic strategy for restoring endothelial function.
Keywords:
Gasdermin DYAPcGASendothelial regenerationinflammationlung injurymitochondrial DNApyroptosisvascular injury

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