PMID- 25911453 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150427 LR - 20181113 IS - 2051-817X (Print) IS - 2051-817X (Electronic) IS - 2051-817X (Linking) VI - 3 IP - 4 DP - 2015 Apr TI - Pericyte NF-kappaB activation enhances endothelial cell proliferation and proangiogenic cytokine secretion in vitro. LID - 10.14814/phy2.12309 [doi] LID - e12309 AB - 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-kappaB), but the downstream effects of NF-kappaB activation on endothelial cell proliferation and cell-cell signaling during repair remain unknown. The purpose of this study was to examine pericyte NF-kappaB activation in a model of skeletal muscle damage; and use genetic manipulation to study the effects of changes in pericyte NF-kappaB activation on endothelial cell proliferation and cytokine secretion. We utilized scratch injury to C2C12 cells in coculture with human primary pericytes to assess NF-kappaB activation and monocyte chemoattractant protein-1 (MCP-1) secretion from pericytes and C2C12 cells. We also cocultured endothelial cells with pericytes that expressed genetically altered NF-kappaB activation levels, and then quantified endothelial cell proliferation and screened the conditioned media for secreted cytokines. Pericytes trended toward greater NF-kappaB activation in injured compared to control cocultures (P = 0.085) and in comparison to C2C12 cells (P = 0.079). Second, increased NF-kappaB 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-kappaB 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. CI - (c) 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. FAU - LaBarbera, Katherine E AU - LaBarbera KE AD - Department of Kinesiology, University of Massachusetts Amherst, Amherst, Massachusetts klabarbe@kin.umass.edu. FAU - Hyldahl, Robert D AU - Hyldahl RD AD - Department of Exercise Sciences, Brigham Young University, Provo, Utah. FAU - O'Fallon, Kevin S AU - O'Fallon KS AD - Department of Kinesiology, University of Massachusetts Amherst, Amherst, Massachusetts. FAU - Clarkson, Priscilla M AU - Clarkson PM AD - Department of Kinesiology, University of Massachusetts Amherst, Amherst, Massachusetts. FAU - Witkowski, Sarah AU - Witkowski S AD - Department of Kinesiology, University of Massachusetts Amherst, Amherst, Massachusetts. LA - eng PT - Journal Article PL - United States TA - Physiol Rep JT - Physiological reports JID - 101607800 PMC - PMC4425949 OTO - NOTNLM OT - Cytokine signaling OT - NF-kappaB OT - microvasculature OT - pericyte EDAT- 2015/04/26 06:00 MHDA- 2015/04/26 06:01 PMCR- 2015/04/27 CRDT- 2015/04/26 06:00 PHST- 2015/04/26 06:00 [entrez] PHST- 2015/04/26 06:00 [pubmed] PHST- 2015/04/26 06:01 [medline] PHST- 2015/04/27 00:00 [pmc-release] AID - 3/4/e12309 [pii] AID - 10.14814/phy2.12309 [doi] PST - ppublish SO - Physiol Rep. 2015 Apr;3(4):e12309. doi: 10.14814/phy2.12309.