Downregulation of renal TonEBP in hypokalemic rats.
Hypokalemia causes a significant decrease in the tonicity of the renal medullary interstitium in association with reduced expression of sodium transporters in the distal tubule. We asked whether hypokalemia caused downregulation of the tonicity-responsive enhancer binding protein (TonEBP) transcriptional activator in the renal medulla due to the reduced tonicity. We found that the abundance of TonEBP decreased significantly in the outer and inner medullas of hypokalemic rats. Underlying mechanisms appeared different in the two regions because the abundance of TonEBP mRNA was lower in the outer medulla but unchanged in the inner medulla. Immunohistochemical examination of TonEBP revealed cell type-specific differences. TonEBP expression decreased dramatically in the outer and inner medullary collecting ducts, thick ascending limbs, and interstitial cells. In the descending and ascending thin limbs, TonEBP abundance decreased modestly. In the outer medulla, TonEBP shifted to the cytoplasm in the descending thin limbs. As expected, transcription of aldose reductase, a target of TonEBP, was decreased since the abundance of mRNA and protein was reduced. Downregulation of TonEBP appeared to have also contributed to reduced expression of aquaporin-2 and UT-A urea transporters in the renal medulla. In cultured cells, expression and activity of TonEBP were not affected by reduced potassium concentrations in the medium. These data support the view that medullary tonicity regulates expression and nuclear distribution of TonEBP in the renal medulla in cell type-specific manners.
Jeon
Un Sil
US
Dept. of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Han
Ki-Hwan
KH
Park
Soo-Hyun
SH
Lee
Sang Do
SD
Sheen
Mee Rie
MR
Jung
Ju-Young
JY
Kim
Wan Young
WY
Sands
Jeff M
JM
Kim
Jin
J
Kwon
H Moo
HM
D000818:Animals; D051399:Aquaporin 2 / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004285:Dogs; D015536:Down-Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D007008:Hypokalemia / Q000201:enzymology / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000096:biosynthesis*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D017419:Potassium, Dietary / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D000096982:Urea Transporters
D051399:Aquaporin 2; D018840:HSP70 Heat-Shock Proteins; D026901:Membrane Transport Proteins; D050778:NFATC Transcription Factors; D024661:Potassium Channels, Inwardly Rectifying; D017419:Potassium, Dietary; D012333:RNA, Messenger; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D000096982:Urea Transporters; C496025:Aqp2 protein, rat; C510692:Kcnj1 protein, rat; C578716:Slc12a1 protein, rat