Na+/Ca2+ exchangers regulate the migration and proliferation of human gastric myofibroblasts

L. Kemény, Andrea Schnúr, Mátyás Czepán, Z. Rakonczay, Eleonóra Gál, J. Lonovics, G. Lazar, Zsolt Simonka, V. Venglovecz, József Maléth, Linda Judák, István B. Németh, Kornélia Szabó, János Almássy, L. Virág, Andrea Geisz, L. Tiszlavicz, David I. Yule, T. Wittmann, Andrea VarróP. Hegyi

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 insulinlike 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume305
Issue number8
DOIs
Publication statusPublished - Oct 15 2013

Fingerprint

Myofibroblasts
Stomach
Homeostasis
Stomach Diseases
Ulcer
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Inflammation
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Calcium oscillation
  • Human myofibroblast
  • Sodium-calcium exchanger

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology
  • Medicine(all)

Cite this

Na+/Ca2+ exchangers regulate the migration and proliferation of human gastric myofibroblasts. / Kemény, L.; Schnúr, Andrea; Czepán, Mátyás; Rakonczay, Z.; Gál, Eleonóra; Lonovics, J.; Lazar, G.; Simonka, Zsolt; Venglovecz, V.; Maléth, József; Judák, Linda; Németh, István B.; Szabó, Kornélia; Almássy, János; Virág, L.; Geisz, Andrea; Tiszlavicz, L.; Yule, David I.; Wittmann, T.; Varró, Andrea; Hegyi, P.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 305, No. 8, 15.10.2013.

Research output: Contribution to journalArticle

Kemény, L. ; Schnúr, Andrea ; Czepán, Mátyás ; Rakonczay, Z. ; Gál, Eleonóra ; Lonovics, J. ; Lazar, G. ; Simonka, Zsolt ; Venglovecz, V. ; Maléth, József ; Judák, Linda ; Németh, István B. ; Szabó, Kornélia ; Almássy, János ; Virág, L. ; Geisz, Andrea ; Tiszlavicz, L. ; Yule, David I. ; Wittmann, T. ; Varró, Andrea ; Hegyi, P. / Na+/Ca2+ exchangers regulate the migration and proliferation of human gastric myofibroblasts. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2013 ; Vol. 305, No. 8.
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AU - Kemény, L.

AU - Schnúr, Andrea

AU - Czepán, Mátyás

AU - Rakonczay, Z.

AU - Gál, Eleonóra

AU - Lonovics, J.

AU - Lazar, G.

AU - Simonka, Zsolt

AU - Venglovecz, V.

AU - Maléth, József

AU - Judák, Linda

AU - Németh, István B.

AU - Szabó, Kornélia

AU - Almássy, János

AU - Virág, L.

AU - Geisz, Andrea

AU - Tiszlavicz, L.

AU - Yule, David I.

AU - Wittmann, T.

AU - Varró, Andrea

AU - Hegyi, P.

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N2 - 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 insulinlike 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.

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