title: Na+/Ca2+ exchangers regulate the migration and proliferation of human gastric myofibroblasts.
abstract: Gastrointestinal myofibroblasts are contractile, electrically nonexcitable, transitional cells that play a role in extracellular matrix production, in ulcer healing, and in pathophysiological conditions they contribute to chronic inflammation and tumor development. Na+/Ca2+ exchangers (NCX) are known to have a crucial role in Ca2+ homeostasis of contractile cells, however, no information is available concerning the role of NCX in the proliferation and migration of gastrointestinal myofibroblasts. In this study, our aim was to investigate the role of NCX in the Ca2+ homeostasis, migration, and proliferation of human gastrointestinal myofibroblasts, focusing on human gastric myofibroblasts (HGMs). We used microfluorometric measurements to investigate the intracellular Ca2+ and Na+ concentrations, PCR analysis and immunostaining to show the presence of the NCX, patch clamp for measuring NCX activity, and proliferation and migration assays to investigate the functional role of the exchanger. We showed that 53.0±8.1% of the HGMs present Ca2+ oscillations, which depend on extracellular Ca2+ and Na+, and can be inhibited by NCX inhibitors. NCX1, NCX2, and NCX3 were expressed at both mRNA and protein levels in HGMs, and they contribute to the intracellular Ca2+ and Na+ homeostasis as well, regardless of the oscillatory activity. NCX inhibitors significantly blocked the basal and insulin-like growth factor II-stimulated migration and proliferation rates of HGMs. In conclusion, we showed that NCX plays a pivotal role in regulating the Ca2+ homeostasis, migration, and proliferation of HGMs. The inhibition of NCX activity may be a potential therapeutic target in hyperproliferative gastric diseases.
authors.affiliation: First Dept. of Medicine, Univ. of Szeged, H-6720, Korányi fasor 8-10, Szeged, Hungary. hegyi.peter@med.u-szeged.hu.
authors.forename: Lajos V
authors.initials: LV
authors.lastname: Kemény
authors.forename: Andrea
authors.initials: A
authors.lastname: Schnúr
authors.forename: Mátyás
authors.initials: M
authors.lastname: Czepán
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: Eleonóra
authors.initials: E
authors.lastname: Gál
authors.forename: János
authors.initials: J
authors.lastname: Lonovics
authors.forename: György
authors.initials: G
authors.lastname: Lázár
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Simonka
authors.forename: Viktória
authors.initials: V
authors.lastname: Venglovecz
authors.forename: József
authors.initials: J
authors.lastname: Maléth
authors.forename: Linda
authors.initials: L
authors.lastname: Judák
authors.forename: István B
authors.initials: IB
authors.lastname: Németh
authors.forename: Kornélia
authors.initials: K
authors.lastname: Szabó
authors.forename: János
authors.initials: J
authors.lastname: Almássy
authors.forename: László
authors.initials: L
authors.lastname: Virág
authors.forename: Andrea
authors.initials: A
authors.lastname: Geisz
authors.forename: László
authors.initials: L
authors.lastname: Tiszlavicz
authors.forename: David I
authors.initials: DI
authors.lastname: Yule
authors.forename: Tibor
authors.initials: T
authors.lastname: Wittmann
authors.forename: Andrea
authors.initials: A
authors.lastname: Varró
authors.forename: Péter
authors.initials: P
authors.lastname: Hegyi
mesh_terms: D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D058628:Myofibroblasts / Q000166:cytology* / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D013270:Stomach / Q000166:cytology*
chemical_list: D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium
keywords: calcium oscillation; human myofibroblast; sodium-calcium exchanger