Open AccessHuman Dermal Microvascular Endothelial Cells Produce Nerve Growth Factor: Implications for Wound Repair
Author(s) -
Nicole S. Gibran,
Ryuichi Tamura,
Ray Tsou,
F. Frank Isik
Publication year - 2003
Publication title -
shock
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/00024382-200302000-00007
Subject(s) - nerve growth factor , neurotrophin , regeneration (biology) , substance p , microbiology and biotechnology , epidermis (zoology) , sensory nerve , dermis , wound healing , angiogenesis , neuropeptide , endothelial stem cell , neurogenic inflammation , chemistry , biology , anatomy , sensory system , medicine , immunology , neuroscience , receptor , biochemistry , in vitro
Following cutaneous injury, sensory nerves regenerate into the dermis and epidermis. Tissues that are innervated by sensory nerves synthesize neurotrophins such as nerve growth factor (NGF). The close anatomic proximity of nerves and capillaries throughout the skin suggests that mutual regulation may exist between nerve fibers and microvascular endothelial cells (MECs) during wound repair. Release of the neuropeptide substance P by sensory nerves induces endothelial cell rounding, capillary leak, and cytokine upregulation. We propose that dermal endothelial cells produce neurotrophins required for nerve fiber maintenance and regeneration. In this study, we demonstrate that substance P stimulates NGF messenger RNA expression by cultured human dermal MECs. Likewise, enzyme-linked immunosorbant assay demonstrated that conditioned medium from cultured dermal MECs contains NGF. NGF bioactivity in the supemates was verified by conditioned medium-induced clonal rat pheochromocytoma (PC-12) cell differentiation. This activity was inhibited by anti-NGF antibodies. Therefore, we have demonstrated that substance P, an inflammatory neuropeptide released by sensory nerve fibers, induces endothelial cells to produce NGF. Our data suggest that MECs may be unrecognized contributors to nerve regeneration after cutaneous injury.