title: KCl Mediates K(+) Channel-Activated Mitogen-Activated Protein Kinases Signaling in Wound Healing.
abstract: BACKGROUND
  Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. K(+) channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether K(+) channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing.
  
  
  METHODS
  The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether K(+) ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot.
  
  
  RESULTS
  The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors.
  
  
  CONCLUSIONS
  Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the K(+) ion channel.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lim
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Byeong Kyu
authors.initials: BK
authors.lastname: Kim
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Suk Wha
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Choi
keywords: Angiogenesis; Mitogen activated protein kinases; Potassium channels; Wound healing