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- W2095542238 abstract "Introduction: Traditional pro-angiogenic molecular switches focus on controlling endothelial cell biology. As a new approach relevant to wound healing, we study how Notch signaling affects the biological responses of cutaneous fibroblasts and their ability to regulate angiogenesis. Methods: Notch signaling status in active versus quiescent human cutaneous fibroblasts was analyzed with RT2-PCRArray and qPCR by detecting Notch receptors, ligands and target genes. Fibroblasts were engineered with viral-vectors to activate Notch pathways (lacZ/vector, control). Production of soluble factors by engineered-fibroblasts was examined using ProteinArrays. The role of Notch-engineered fibroblasts in regulating angiogenesis was analyzed in three-dimensional angiogenesis in vitro models and the in vivo subcutaneous Matrigel® plug assay (N=15). Specificity was confirmed by antagonist and factor replacement studies. Data was analyzed by ANOVA. Results: Quiescentfibroblasts overexpress Notch pathway components while actively proliferating fibroblasts down-regulate Notch signaling.Enforced activation of Notch signaling inhibits fibroblast proliferation and migration by 30% and 58% respectively and decreases IL-6 production by 2-folds (P<0.05). Angiogenesis is significantly inhibited in vitro and in vivo by Notch-engineered fibroblasts. The downregulation of IL-6 is in part responsible for this inhibitory effect, as replacement of IL-6 rescues the angiogenic defect, both in vitro and in vivo. Conclusions: Modulation of Notch signaling in human cutaneous fibroblasts is identified as a novel approach for regulating the angiogenic response. While the status of Notch signaling in human skin wounds requires formal study, quiescent cutaneous fibroblasts and decreased angiogenesis are features of non-healing wounds which makes our findings relevant to the wound healing field." @default.
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- W2095542238 date "2011-02-01" @default.
- W2095542238 modified "2023-09-27" @default.
- W2095542238 title "Modulation Of NOTCH Signaling In Cutaneous Fibroblasts To Regulate Angiogenesis" @default.
- W2095542238 doi "https://doi.org/10.1016/j.jss.2010.11.489" @default.
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