Arch Plast Surg.  2015 Jan;42(1):11-19. 10.5999/aps.2015.42.1.11.

KCl Mediates K+ Channel-Activated Mitogen-Activated Protein Kinases Signaling in Wound Healing

• Shim JH
• Lim JW
• Kim BK
• Park SJ
• Kim SW
• Choi TH

• KMID: 2267588
• DOI: http://doi.org/10.5999/aps.2015.42.1.11

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.

Keyword

Potassium channels; Mitogen activated protein kinases; Wound healing; Angiogenesis

MeSH Terms

Blotting, Western
Cell Count
Cell Line
Cell Survival
Collagen
Fibroblast Growth Factor 2
Fibroblasts
Humans
Inflammation
Ion Channels
Mitogen-Activated Protein Kinases*
Phosphorylation
Phosphotransferases
Potassium Channels
Potassium Chloride
Protein Kinases
Skin
Thrombospondin 1
Vascular Endothelial Growth Factor A
Wound Healing*
Collagen
Fibroblast Growth Factor 2
Ion Channels
Mitogen-Activated Protein Kinases
Phosphotransferases
Potassium Channels
Potassium Chloride
Protein Kinases
Thrombospondin 1
Vascular Endothelial Growth Factor A