TY - JOUR
T1 - KCNA1 and TRPC6 ion channels and NHE1 exchanger operate the biological outcome of HGF/scatter factor in renal tubular cells
AU - Rampino, Teresa
AU - Gregorini, Marilena
AU - Guidetti, Cristina
AU - Broggini, Massimo
AU - Marchini, Sergio
AU - Bonomi, Riccardo
AU - Maggio, Milena
AU - Roscini, Elisabetta
AU - Soccio, Grazia
AU - Tiboldo, Renza
AU - Dal Canton, Antonio
PY - 2007/12
Y1 - 2007/12
N2 - Hepatocyte growth factor (HGF) is a glycoprotein that induces in vitro epithelial tubular cell growth, motility, scattering and branching morphogenesis. The cell machineries that account for HGF biological effects are still unclear. In previous study, we found that HGF upregulated in epithelial tubular cell line (HK2) 3 genes: potassium channel KCNA1, calcium channel (transient receptor potential channel, subfamily C, member 6, TRPC6) and Na+/H+ exchanger-1 (NHE1). In this study, we validated these results with reverse transcription PCR and WB analysis. To investigate whether KCNA1, TRPC6, NHE1 mediate the changes induced by HGF in HK2, we studied the effects of their inhibitors: 4-aminopyridine, charybdotoxin, dendrotoxin K inhibitors of KCNA1, lanthanum, N-(p-amylcinnamoyl) anthranilic acid inhibitors of TRPC6, 5-(N-ethyl-N-isopropyl)amiloride, cariporide inhibitors of NHE1. The inhibitors prevented HGF-induced growth, migration, cytoskeletal reorganization and tubulogenesis in HK2. These results indicate that KCNA1, TRPC6 and NHE1 are cell machineries that are exploited by HGF to effect its biological outcome in renal tubular cells.
AB - Hepatocyte growth factor (HGF) is a glycoprotein that induces in vitro epithelial tubular cell growth, motility, scattering and branching morphogenesis. The cell machineries that account for HGF biological effects are still unclear. In previous study, we found that HGF upregulated in epithelial tubular cell line (HK2) 3 genes: potassium channel KCNA1, calcium channel (transient receptor potential channel, subfamily C, member 6, TRPC6) and Na+/H+ exchanger-1 (NHE1). In this study, we validated these results with reverse transcription PCR and WB analysis. To investigate whether KCNA1, TRPC6, NHE1 mediate the changes induced by HGF in HK2, we studied the effects of their inhibitors: 4-aminopyridine, charybdotoxin, dendrotoxin K inhibitors of KCNA1, lanthanum, N-(p-amylcinnamoyl) anthranilic acid inhibitors of TRPC6, 5-(N-ethyl-N-isopropyl)amiloride, cariporide inhibitors of NHE1. The inhibitors prevented HGF-induced growth, migration, cytoskeletal reorganization and tubulogenesis in HK2. These results indicate that KCNA1, TRPC6 and NHE1 are cell machineries that are exploited by HGF to effect its biological outcome in renal tubular cells.
KW - Calcium channel
KW - Na/H exchanger-1
KW - Potassium channel
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U2 - 10.1080/08977190801892184
DO - 10.1080/08977190801892184
M3 - Article
C2 - 18365869
AN - SCOPUS:41449095253
VL - 25
SP - 382
EP - 391
JO - Growth Factors
JF - Growth Factors
SN - 0897-7194
IS - 6
ER -