Differentiation state determines neural effects on microvascular endothelial cells.
Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells.
University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104, USA. muffley@u.washington.edu
Lara A
LA
Muffley
Shin-Chen
SC
Pan
Andria N
AN
Smith
Maricar
M
Ga
Anne M
AM
Hocking
Nicole S
NS
Gibran
D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D015194:Diffusion Chambers, Culture; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D055806:Microvessels / Q000166:cytology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D009928:Organ Specificity; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*
D015415:Biomarkers; D009569:Nitric Oxide