title: Tumor Necrosis Factor α Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB.
abstract: 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.
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI, USA.
authors: Anthony R
authors: AR
authors: Prisco
authors: Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI, USA.|Department of Medicine, Division of Cardiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Medical College of Wisconsin, Cardiovascular Center, Milwaukee, WI, USA.
authors: Brian R
authors: BR
authors: Hoffmann
authors: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA.
authors: Catherine C
authors: CC
authors: Kaczorowski
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Medical College of Wisconsin, Human and Molecular Genetics Center, Milwaukee, WI, USA.
authors: Chris
authors: C
authors: McDermott-Roe
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI, USA.
authors: Timothy J
authors: TJ
authors: Stodola
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI, USA.
authors: Eric C
authors: EC
authors: Exner
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI, USA.
authors: Andrew S
authors: AS
authors: Greene
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000075982:Cell Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002853:Chromatography, Liquid; D004558:Electric Stimulation; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000075982:Cell Adhesion Molecule-1; D008565:Membrane Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha
keywords: CADM1; Cellular migration; Endothelial progenitor cells; TNFα