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Updated: Jun 3, 2026
04:23
Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells
Published on: March 31, 2021
The κ opioid system regulates endothelial cell differentiation and pathfinding in vascular development
Kohei Yamamizu1, Sadayoshi Furuta, Shiori Katayama
1Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Blood
|April 5, 2011
Summary
The kappa opioid system (KOR) inhibits vascular development by suppressing cAMP/PKA signaling, impacting endothelial cell differentiation and vascular pathfinding. This reveals a novel role for opioids in regulating blood vessel formation.
Area of Science:
- Molecular Biology
- Developmental Biology
- Neuroscience
Background:
- The opioid system regulates neurophysiologic functions, including pain control.
- Previous research indicated cAMP/protein kinase A (PKA) signaling enhances vascular progenitor differentiation into endothelial cells (ECs).
- Kappa opioid receptor (KOR) is expressed in vascular progenitors and is an inhibitory G protein-coupled receptor.
Purpose of the Study:
- To investigate novel roles of the kappa opioid system in vascular development.
- To elucidate the mechanism by which KOR influences endothelial cell differentiation and vascular formation.
- To examine the impact of KOR signaling on vascular pathfinding.
Main Methods:
- Utilized embryonic stem cell-derived Flk1(+) vascular progenitors.
- Administered KOR agonists and measured effects on EC differentiation and gene expression (Flk1, Neuropilin1/NRP1).
- Investigated KOR-null and dynorphin-null mice to assess in vivo vascular formation and pathfinding.
Main Results:
- KOR agonists inhibited EC differentiation and 3D vascular formation by decreasing Flk1 and NRP1 expression.
- KOR activation suppressed cAMP/PKA signaling, as effects were reversed by cAMP or PKA agonists.
- KOR-null mice exhibited increased vascular formation and ectopic vascular invasion, with altered Flk1, NRP1, and plexinD1 expression.
Conclusions:
- The kappa opioid system is a novel regulator of vascular development.
- KOR influences both endothelial cell differentiation and vascular pathfinding.
- Opioid signaling modulates vascular properties through the cAMP/PKA pathway and affects plexinD1 expression.
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