Premium
TNFα regulates endothelial progenitor cell migration through the NF‐κB pathway (1180.16)
Author(s) -
Prisco Anthony,
Hoffmann Brian,
Kaczorowski Catherine,
Greene Andrew
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1180.16
Subject(s) - matrigel , progenitor cell , bone marrow , microbiology and biotechnology , endothelial progenitor cell , regeneration (biology) , medicine , gene knockdown , tumor necrosis factor alpha , cancer research , endothelial stem cell , stem cell , angiogenesis , immunology , chemistry , in vitro , biology , apoptosis , biochemistry
Many therapies exist to treat myocardial infarctions (MI). Most current therapies focus on management of symptoms rather than regeneration of tissue. Cardiac function has been improved in rodents using bone marrow derived endothelial progenitor cells (EPCs) as a regenerative therapeutic, however human studies have produced inconsistent results as regenerative mechanisms are poorly understood. For an injected EPC to improve cardiac function, the cell must migrate, bind and engraft within the damaged tissue. EPCs are mobilized from the bone marrow to the circulation following MI. One of the inflammatory cytokines released in an MI is TNFα. We hypothesized that an acute dose of TNFα would induce EPC migration toward vessel like structures in vitro. To test this hypothesis, endothelial cells were plated onto a 4 well chamber slide coated with Matrigel substrate to grow vessel‐like structures. After 48 hours, EPCs were treated with TNFα or vehicle and added to the wells containing vessel‐like structures. After tracking the EPCs for 16 hours, a significantly higher fraction of EPCs treated with TNFα than vehicle were found to have migrated towards vessel like structures. Follow up analysis demonstrated that the migratory phenotype was mediated through the NF‐κB pathway, simulated by the TNF Receptor 2. Proteomic analysis suggested several NF‐κB transcriptional targets that were directly tested using siRNA knockdown. Grant Funding Source : NIH Grant HL082798