title: Electric current-induced lymphatic activation.
abstract: The lymphatic system in skin plays important roles in drainage of wastes and in the afferent phase of immune response. We previously showed that activation of vascular endothelial growth factor receptor (VEGFR), specifically the VEGFC/VEGFR-3 pathway, attenuates oedema and inflammation by promoting lymphangiogenesis, suggesting a protective role of lymphatic vessels against skin inflammation. However, it remains unknown how physical stimuli promote lymphatic function. Here, we show that lymphatic endothelial cells (LECs) are activated by direct-current (DC) electrical stimulation, which induced extension of actin filaments of LECs, increased calcium influx into LECs, and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK). An inhibitor of focal adhesion kinase, which plays a role in cellular adhesion and motility, diminished the DC-induced extension of F-actin and abrogated p38 phosphorylation. Time-lapse imaging revealed that pulsed-DC stimulation promoted proliferation and migration of LECs. Overall, these results indicate that electro-stimulation activates lymphatic function by activating p38 MAPK.
authors.affiliation: Shiseido Research Center, Yokohama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kajiya
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsumoto-Okazaki
authors.forename: Mika
authors.initials: M
authors.lastname: Sawane
authors.forename: Kaedeko
authors.initials: K
authors.lastname: Fukada
authors.forename: Yuya
authors.initials: Y
authors.lastname: Takasugi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Akai
authors.forename: Naoki
authors.initials: N
authors.lastname: Saito
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Mori
mesh_terms: D020013:Calcium Signaling; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology; D004558:Electric Stimulation; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000502:physiology; D006801:Humans
chemical_list: D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: calcium influx; direct current; lymphatic