Open AccessPericyte NF ‐ κ B activation enhances endothelial cell proliferation and proangiogenic cytokine secretion in vitro
Author(s) -
LaBarbera Katherine E.,
Hyldahl Robert D.,
O'Fallon Kevin S.,
Clarkson Priscilla M.,
Witkowski Sarah
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12309
Subject(s) - pericyte , microbiology and biotechnology , cytokine , endothelial stem cell , c2c12 , secretion , angiogenesis , cell growth , biology , nf κb , signal transduction , chemistry , myocyte , immunology , cancer research , myogenesis , in vitro , endocrinology , biochemistry
Pericytes are skeletal muscle resident, multipotent stem cells that are localized to the microvasculature. In vivo, studies have shown that they respond to damage through activation of nuclear‐factor kappa‐B ( NF ‐ κ B), but the downstream effects of NF ‐ κ B activation on endothelial cell proliferation and cell–cell signaling during repair remain unknown. The purpose of this study was to examine pericyte NF ‐ κ B activation in a model of skeletal muscle damage; and use genetic manipulation to study the effects of changes in pericyte NF ‐ κ B activation on endothelial cell proliferation and cytokine secretion. We utilized scratch injury to C 2 C 12 cells in coculture with human primary pericytes to assess NF ‐ κ B activation and monocyte chemoattractant protein‐1 ( MCP ‐1) secretion from pericytes and C 2 C 12 cells. We also cocultured endothelial cells with pericytes that expressed genetically altered NF ‐ κ B activation levels, and then quantified endothelial cell proliferation and screened the conditioned media for secreted cytokines. Pericytes trended toward greater NF ‐ κ B activation in injured compared to control cocultures ( P = 0.085) and in comparison to C 2 C 12 cells ( P = 0.079). Second, increased NF ‐ κ B activation in pericytes enhanced the proliferation of cocultured endothelial cells (1.3‐fold, P = 0.002). Finally, we identified inflammatory signaling molecules, including MCP ‐1 and interleukin 8 ( IL ‐8) that may mediate the crosstalk between pericytes and endothelial cells. The results of this study show that pericyte NF ‐ κ B activation may be an important mechanism in skeletal muscle repair with implications for the development of therapies for musculoskeletal and vascular diseases, including peripheral artery disease.