KCNA1 and TRPC6 ion channels and NHE1 exchanger operate the biological outcome of HGF/scatter factor in renal tubular cells.
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.
Rampino
Teresa
T
Unit of Nephrology, Dialysis and Transplantation, Fondazione, IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy.
Gregorini
Marilena
M
Guidetti
Cristina
C
Broggini
Massimo
M
Marchini
Sergio
S
Bonomi
Riccardo
R
Maggio
Milena
M
Roscini
Elisabetta
E
Soccio
Grazia
G
Tiboldo
Renza
R
Dal Canton
Antonio
A
D002121:Calcium Channel Blockers / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007684:Kidney Tubules / Q000166:cytology; D051662:Kv1.1 Potassium Channel / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015398:Signal Transduction; D026941:Sodium Channel Blockers / Q000494:pharmacology; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D050052:TRPC Cation Channels / Q000502:physiology*; D000074287:TRPC6 Cation Channel
D002121:Calcium Channel Blockers; D027682:Cation Transport Proteins; C066855:HGF protein, human; C496946:KCNA1 protein, human; D026902:Potassium Channel Blockers; C490998:SLC9A1 protein, human; D026941:Sodium Channel Blockers; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D051662:Kv1.1 Potassium Channel; D017228:Hepatocyte Growth Factor