Epidermal growth factor regulation of rat NHE2 gene expression.
Epidermal growth factor (EGF) is involved in acute regulation of Na(+)/H(+) exchangers (NHEs), but the effect of chronic EGF administration on NHE gene expression is unknown. The present studies showed that EGF treatment increased NHE2-mediated intestinal brush-border membrane vesicle Na(+) absorption and NHE2 mRNA abundance by nearly twofold in 19-day-old rats. However, no changes were observed in renal NHE2 mRNA or intestinal and renal NHE3 mRNA abundance. To understand the mechanism of this regulation, we developed the rat intestinal epithelial (RIE) cell as an in vitro model to study the effect of EGF on NHE2 gene expression. EGF increased functional NHE2 activity and mRNA abundance in cultured RIE cells, and this stimulation could be blocked by actinomycin D (a transcriptional inhibitor). Additionally, NHE2 promoter reporter gene assays in transiently transfected RIE cells showed an almost twofold increase in promoter activity after EGF treatment. We conclude that rat NHE2 activity can be stimulated by chronic EGF treatment and that this response is at least partially mediated by gene transcription.
Xu
H
H
Departments of Pediatrics, Steele Memorial Children's Research Center, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA. fgishan@peds.arizona.edu
Collins
J F
JF
Bai
L
L
Kiela
P R
PR
Lynch
R M
RM
Ghishan
F K
FK
D000818:Animals; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; C513110:Slc9a2 protein, rat; C000613387:Slc9a3 protein, rat; C081518:Slc9a4 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D003609:Dactinomycin; D004815:Epidermal Growth Factor