NHE1 activity contributes to migration and is necessary for proliferation of human gastric myofibroblasts

Mátyás Czepán, Z. Rakonczay, Andrea Varró, Islay Steele, Rod Dimaline, Nantaporn Lertkowit, J. Lonovics, Andrea Schnúr, György Biczó, Andrea Geisz, G. Lazar, Zsolt Simonka, V. Venglovecz, T. Wittmann, P. Hegyi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Myofibroblasts play central roles in wound healing, deposition of the extracellular matrix and epithelial function. Their functions depend on migration and proliferation within the subepithelial matrix, which results in accelerated cellular metabolism. Upregulated metabolic pathways generate protons which need to be excreted to maintain intracellular pH (pHi). We isolated human gastric myofibroblasts (HGMs) from surgical specimens of five patients. Then we characterized, for the first time, the expression and functional activities of the Na +/H + exchanger (NHE) isoforms 1, 2 and 3, and the functional activities of the Na +/HCO 3 - cotransporter (NBC) and the anion exchanger (AE) in cultured HGMs using microfluorimetry, immunocytochemistry, reverse transcription polymerase chain reaction and immunoblot analysis. We showed that NHE1-3, NBC and AE activities are present in HGMs and that NHE1 is the most active of the NHEs. In scratch wound assays we also demonstrated (using the selective NHE inhibitor HOE-642) that carbachol and insulin like growth factor II (IGF-II) partly stimulate migration of HGMs in a NHE1-dependent manner. EdU incorporation assays revealed that IGF-II induces proliferation of HGMs which is inhibited by HOE-642. The results indicate that NHE1 is necessary for IGF-II-induced proliferation response of HGMs. Overall, we have characterized the pHi regulatory mechanisms of HGMs. In addition, we demonstrated that NHE1 activity contributes to both IGF-II- and carbachol-stimulated migration and that it is obligatory for IGF-II-induced proliferation of HGMs.

Original languageEnglish
Pages (from-to)459-475
Number of pages17
JournalPflugers Archiv European Journal of Physiology
Volume463
Issue number3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Insulin-Like Growth Factor II
Myofibroblasts
Stomach
Sodium-Hydrogen Antiporter
Carbachol
Anions
Assays
Polymerase chain reaction
Transcription
Metabolism
Protons
Protein Isoforms
Chloride-Bicarbonate Antiporters
Cytophotometry
Metabolic Networks and Pathways
Wound Healing
Reverse Transcription
Extracellular Matrix
Immunohistochemistry
Polymerase Chain Reaction

Keywords

  • Fibroblast
  • Gastrointestinal tract
  • Human
  • Na /H exchange

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)
  • Medicine(all)

Cite this

NHE1 activity contributes to migration and is necessary for proliferation of human gastric myofibroblasts. / Czepán, Mátyás; Rakonczay, Z.; Varró, Andrea; Steele, Islay; Dimaline, Rod; Lertkowit, Nantaporn; Lonovics, J.; Schnúr, Andrea; Biczó, György; Geisz, Andrea; Lazar, G.; Simonka, Zsolt; Venglovecz, V.; Wittmann, T.; Hegyi, P.

In: Pflugers Archiv European Journal of Physiology, Vol. 463, No. 3, 03.2012, p. 459-475.

Research output: Contribution to journalArticle

Czepán, Mátyás ; Rakonczay, Z. ; Varró, Andrea ; Steele, Islay ; Dimaline, Rod ; Lertkowit, Nantaporn ; Lonovics, J. ; Schnúr, Andrea ; Biczó, György ; Geisz, Andrea ; Lazar, G. ; Simonka, Zsolt ; Venglovecz, V. ; Wittmann, T. ; Hegyi, P. / NHE1 activity contributes to migration and is necessary for proliferation of human gastric myofibroblasts. In: Pflugers Archiv European Journal of Physiology. 2012 ; Vol. 463, No. 3. pp. 459-475.
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AU - Czepán, Mátyás

AU - Rakonczay, Z.

AU - Varró, Andrea

AU - Steele, Islay

AU - Dimaline, Rod

AU - Lertkowit, Nantaporn

AU - Lonovics, J.

AU - Schnúr, Andrea

AU - Biczó, György

AU - Geisz, Andrea

AU - Lazar, G.

AU - Simonka, Zsolt

AU - Venglovecz, V.

AU - Wittmann, T.

AU - Hegyi, P.

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KW - Gastrointestinal tract

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