Chemokine mediated signalling within arteries promotes vascular smooth muscle cell recruitment
| Autor: | Marina Venero Galanternik, Olivia Farrelly, Lauren M. Goddard, Yoh-suke Mukouyama, Oliver Nguyen, Timothy J Bolan, Margaret C Burns, Brant M. Weinstein, Joseph J Yano, Daniel Castranova, Amber N. Stratman, Van N. Pham, Andrew M. Davis, Wenling Li, Mark L. Kahn |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Chemokine Receptors CXCR4 Vascular smooth muscle Myocytes Smooth Muscle Medicine (miscellaneous) 030204 cardiovascular system & hematology General Biochemistry Genetics and Molecular Biology Article Muscle Smooth Vascular Animals Genetically Modified 03 medical and health sciences Mice 0302 clinical medicine Morphogenesis Animals Autocrine signalling Receptor Zebrafish Transcription factor PDGFB biology Chemistry Chemotaxis biology.organism_classification Cell biology 030104 developmental biology Mutation biology.protein cardiovascular system Angiogenesis CRISPR-Cas Systems Chemokines General Agricultural and Biological Sciences Cell signalling Signal Transduction |
| Zdroj: | Communications Biology |
| ISSN: | 2399-3642 |
| Popis: | The preferential accumulation of vascular smooth muscle cells (vSMCs) on arteries versus veins during early development is a well-described phenomenon, but the molecular pathways underlying this polarization are not well understood. In zebrafish, the cxcr4a receptor (mammalian CXCR4) and its ligand cxcl12b (mammalian CXCL12) are both preferentially expressed on arteries at time points consistent with the arrival and differentiation of the first vSMCs during vascular development. We show that autocrine cxcl12b/cxcr4 activity leads to increased production of the vSMC chemoattractant ligand pdgfb by endothelial cells in vitro and increased expression of pdgfb by arteries of zebrafish and mice in vivo. Additionally, we demonstrate that expression of the blood flow-regulated transcription factor klf2a in primitive veins negatively regulates cxcr4/cxcl12 and pdgfb expression, restricting vSMC recruitment to the arterial vasculature. Together, this signalling axis leads to the differential acquisition of vSMCs at sites where klf2a expression is low and both cxcr4a and pdgfb are co-expressed, i.e. arteries during early development. Stratman et al. provide evidence linking the cxcl12b/cxcr4a signaling axis in endothelial cells to an increased release of platelet-derived growth factor b, leading to the recruitment of smooth muscle cells to developing arteries. This signalling axis is suppressed in the venous endothelium during early development by the high expression of blood flow-regulated transcription factor klf2a. |
| Databáze: | OpenAIRE |
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