EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration.
AQP3 (aquaporin-3), known as an integral membrane channel in epidermal keratinocytes, facilitates water and glycerol movement into and out of the skin. Here, we demonstrate that AQP3 is also expressed in cultured human skin fibroblasts, which under normal wound healing processes migrate from surrounding tissues to close the wound. EGF (epidermal growth factor), which induced fibroblast migration, also induced AQP3 expression in a time- and dose-dependent manner. CuSO4 and NiCl2, previously known as AQP3 water transport inhibitors, as well as two other bivalent heavy metals Mn2+ and Co2+, inhibited EGF-induced cell migration in human skin fibroblasts. AQP3 knockdown by small interfering RNA inhibited EGF-induced AQP3 expression and cell migration. Furthermore, an EGFR (EGF receptor) kinase inhibitor, PD153035, blocked EGF-induced AQP3 expression and cell migration. MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK inhibitor U0126 and PI3K (phosphoinositide 3-kinase) inhibitor LY294002 also inhibited EGF-induced AQP3 expression and cell migration. Collectively, our findings show for the first time that AQP3 is expressed in human skin fibroblasts and that EGF induces AQP3 expression via EGFR, PI3K and ERK signal transduction pathways. We have provided evidence for a novel role of AQP3 in human skin fibroblast cell migration, which occurs during normal wound healing.
Cao
Cong
C
Department of Biology, Providence College, 549 River Ave., Providence, RI 02918, USA.
Sun
Yun
Y
Healey
Sarah
S
Bi
Zhigang
Z
Hu
Gang
G
Wan
Shu
S
Kouttab
Nicola
N
Chu
Wenming
W
Wan
Yinsheng
Y
D051400:Aquaporin 3 / Q000096:biosynthesis* / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013431:Sulfates / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
C496027:AQP3 protein, human; D013431:Sulfates; D051400:Aquaporin 3; D004815:Epidermal Growth Factor; C022838:nickel chloride; D009532:Nickel; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases