Expression and regulation of the Na(+)/K(+)/2Cl(-) cotransporter NKCC1 in rat liver and human HuH-7 hepatoma cells.
The expression of sodium potassium chloride cotransporter 1 (NKCC1) was studied in different liver cell types. NKCC1 was found in rat liver parenchymal and sinusoidal endothelial cells and in human HuH-7 hepatoma cells. NKCC1 expression in rat hepatic stellate cells increased during culture-induced transformation in the myofibroblast-like phenotype. NKCC1 inhibition by bumetanide increased alpha(1)-smooth muscle actin expression in 2-day-cultured hepatic stellate cells but was without effect on basal and platelet-derived-growth-factor-induced proliferation of the 14-day-old cells. In perfused rat liver the NKCC1 made a major contribution to volume-regulatory K(+) uptake induced by hyperosmolarity. Long-term hyperosmotic treatment of HuH-7 cells by elevation of extracellular NaCl or raffinose concentration but not hyperosmotic urea or mannitol profoundly induced NKCC1 mRNA and protein expression. This was antagonized by the compatible organic osmolytes betaine or taurine. The data suggest a role of NKCC1 in stellate cell transformation, hepatic volume regulation, and long-term adaption to dehydrating conditions.
Schliess
Freimut
F
Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
Schäfer
Christine
C
vom Dahl
Stephan
S
Fischer
Richard
R
Lordnejad
Mohammad R
MR
Häussinger
Dieter
D
D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010477:Perfusion; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics* / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C578877:SLC12A2 protein, human; C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D011188:Potassium