PMID- 16848764 OWN - NLM STAT- MEDLINE DCOM- 20061128 LR - 20181201 IS - 1470-8728 (Electronic) IS - 0264-6021 (Print) IS - 0264-6021 (Linking) VI - 400 IP - 2 DP - 2006 Dec 1 TI - EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. PG - 225-34 AB - 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. FAU - Cao, Cong AU - Cao C AD - Department of Biology, Providence College, 549 River Ave., Providence, RI 02918, USA. FAU - Sun, Yun AU - Sun Y FAU - Healey, Sarah AU - Healey S FAU - Bi, Zhigang AU - Bi Z FAU - Hu, Gang AU - Hu G FAU - Wan, Shu AU - Wan S FAU - Kouttab, Nicola AU - Kouttab N FAU - Chu, Wenming AU - Chu W FAU - Wan, Yinsheng AU - Wan Y LA - eng GR - P20 RR016457/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (AQP3 protein, human) RN - 0 (Sulfates) RN - 158801-98-0 (Aquaporin 3) RN - 62229-50-9 (Epidermal Growth Factor) RN - 696BNE976J (nickel chloride) RN - 7OV03QG267 (Nickel) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM ECI - Biochem J. 2017 Aug 10;474(16):2901-2. PMID: 28798161 MH - Aquaporin 3/*biosynthesis/genetics MH - Cell Movement/drug effects/*physiology MH - Cells, Cultured MH - Drug Interactions MH - Epidermal Growth Factor/antagonists & inhibitors/pharmacology MH - ErbB Receptors/*metabolism MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Fibroblasts/cytology/drug effects/enzymology/metabolism MH - Humans MH - Keratinocytes/cytology/drug effects/enzymology/metabolism MH - Nickel/pharmacology MH - Phosphatidylinositol 3-Kinases/metabolism MH - RNA Interference MH - Signal Transduction/drug effects MH - Skin/*cytology/drug effects/enzymology/*metabolism MH - Sulfates/pharmacology MH - Wound Healing/drug effects/physiology PMC - PMC1652825 EDAT- 2006/07/20 09:00 MHDA- 2006/12/09 09:00 PMCR- 2007/06/01 CRDT- 2006/07/20 09:00 PHST- 2006/07/20 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/07/20 09:00 [entrez] PHST- 2007/06/01 00:00 [pmc-release] AID - BJ20060816 [pii] AID - bj4000225 [pii] AID - 10.1042/BJ20060816 [doi] PST - ppublish SO - Biochem J. 2006 Dec 1;400(2):225-34. doi: 10.1042/BJ20060816.