Tumor Necrosis Factor α Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB. Stem Cells 2016 Jul;34(7):1922-33
Date
02/13/2016Pubmed ID
26867147Pubmed Central ID
PMC4931961DOI
10.1002/stem.2339Scopus ID
2-s2.0-84979011069 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
Shortly after the discovery of endothelial progenitor cells (EPCs) in 1997, many clinical trials were conducted using EPCs as a cellular based therapy with the goal of restoring damaged organ function by inducing growth of new blood vessels (angiogenesis). Results were disappointing, largely because the cellular and molecular mechanisms of EPC-induced angiogenesis were not clearly understood. Following injection, EPCs must migrate to the target tissue and engraft prior to induction of angiogenesis. In this study EPC migration was investigated in response to tumor necrosis factor α (TNFα), a pro-inflammatory cytokine, to test the hypothesis that organ damage observed in ischemic diseases induces an inflammatory signal that is important for EPC homing. In this study, EPC migration and incorporation were modeled in vitro using a coculture assay where TNFα treated EPCs were tracked while migrating toward vessel-like structures. It was found that TNFα treatment of EPCs increased migration and incorporation into vessel-like structures. Using a combination of genomic and proteomic approaches, NF-kB mediated upregulation of CADM1 was identified as a mechanism of TNFα induced migration. Inhibition of NF-kB or CADM1 significantly decreased migration of EPCs in vitro suggesting a role for TNFα signaling in EPC homing during tissue repair. Stem Cells 2016;34:1922-1933.
Author List
Prisco AR, Hoffmann BR, Kaczorowski CC, McDermott-Roe C, Stodola TJ, Exner EC, Greene ASMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Cell Adhesion Molecule-1
Cell Movement
Chromatography, Liquid
Electric Stimulation
Endothelial Progenitor Cells
Gene Knockdown Techniques
Membrane Proteins
NF-kappa B
Neovascularization, Physiologic
Rats, Sprague-Dawley
Receptors, Tumor Necrosis Factor
Signal Transduction
Tandem Mass Spectrometry
Tumor Necrosis Factor-alpha
