2025-11-14 バージニア工科大学(Virginia Tech)
A microscopic image of a blood vessel after the endothelium is damaged. The endothelial cell lining is red; the blood vessels’ walls are green; and the cells’ nuclei are blue. Image courtesy of Scott Johnstone.
<関連情報>
- https://news.vt.edu/articles/2025/11/research_fralinbiomed_johnstonecx43.html
- https://journals.physiology.org/doi/full/10.1152/ajpheart.00153.2025
傷害誘発性コネキシン43発現は内皮創傷治癒を制御する Injury-induced connexin 43 expression regulates endothelial wound healing
Meghan W. Sedovy, Mark C. Renton, Kailynn Roberts, Xinyan Leng, Clare L. Dennison, Caroline O. Toler, Melissa R. Leaf, Paul D. Lampe, Angela K. Best, Brant E. Isakson, and Scott R. Johnstone
Heart and Circulatory Physiology Published:2025 Nov 11
DOI:https://doi.org/10.1152/ajpheart.00153.2025
Abstract
Endothelial cell (EC) injury is a major contributing factor to vascular surgical failure. As such, understanding the mechanisms of endothelial healing is essential to the development of vascular therapeutics and procedures. Gap junctions formed by connexin 43 (Cx43) are implicated in regulating skin wound healing, but their role in endothelial healing is unknown. Secondary analysis of RNA-seq data from in vivo injured mouse aortas (GEO: GSE115618) identified significant Cx43 upregulation in EC postinjury. We developed a novel in vivo model of EC injury using mouse carotid artery ligation to test the role of Cx43. We identified that EC immediately adjacent to the wound edge upregulate Cx43 protein expression, predominantly at cell-cell junctions. We show significantly delayed EC healing in a mouse model of inducible EC-specific Cx43 deletion [EC-Cx43 knockout (KO)] at 24 h post ligation. Single-cell RNA-seq analysis of 10,829 cells from 18 h injured EC-wild type (WT) and EC-Cx43 KO carotids revealed a Cx43-associated reduction in enrichment of EC pathways associated with migration, proliferation, and ERK/MAPK signaling pathways. Finally, the importance of Cx43 phosphorylation on EC healing was tested in mice with single-point alanine mutations (phospho-null) in known phosphorylation sites that alter Cx43 channel assembly and opening. Mice containing alanine mutations at ERK phosphorylated Cx43 serines (Cx43S255/262/279/282A) have reduced healing rates similar to EC-Cx43 KO mice. These data suggest that EC injury-induced Cx43 upregulation and subsequent Cx43 gap junction-mediated cell-to-cell communication are required for normal EC migration during wound healing after vascular injury.
NEW & NOTEWORTHY These findings demonstrate for the first time that mechanical injury to large artery endothelium induces the expression of gap junction protein Cx43. This upregulation improves the migratory and proliferative capacity of endothelial cells at the wound edge, facilitating timely wound closure. This phenomenon is dependent on appropriate gap junction function and turnover.
