Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P51532 (
transcriptional activator
)
6,546
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tonicity-responsive enhancer binding protein
(
TonEBP
) is a
transcriptional activator
of the Rel family. In the renal medulla,
TonEBP
stimulates genes encoding proteins involved in cellular accumulation of organic osmolytes, the vasopressin-regulated urea transporters (UT-A), and heat shock protein 70. To understand the role of
TonEBP
in the development of urinary concentrating ability,
TonEBP
expression during rat kidney development was investigated. In embryonic kidneys,
TonEBP
immunoreactivity was detected 16 days postcoitus in the cytoplasm of the endothelial cells surrounding the medullary collecting ducts (MCD). By 20 days,
TonEBP
was detected in most tubular profiles in the medulla, including the loop of Henle and MCD, and interstitial cells. The intensity of
TonEBP
immunoreactivity was much higher in the vasa recta than the tubules. In addition, immunoreactivity was localized predominantly to the cytoplasm. On postnatal day 1, two major changes were observed.
TonEBP
immunoreactivity shifted to the nucleus, and the intensity of
TonEBP
immunoreactivity of the tubules increased dramatically. These changes were associated with an increase in
TonEBP
and sodium-myo-inositol cotransporter mRNA abundance. Thereafter,
TonEBP
expression in tubular profiles increased moderately. The adult pattern of
TonEBP
expression was established at postnatal day 21 coincident with full maturation of the renal medulla. Thus expression of
TonEBP
in developing kidneys occurred predominantly in the medulla and preceded expression of its target genes, including UT-A. These data suggest that
TonEBP
contributes to the development of urine-concentrating ability.
...
PMID:Maturation of TonEBP expression in developing rat kidney. 1547 42
Tonicity-responsive enhancer binding protein
(
TonEBP
) is a
transcriptional activator
that is regulated by ambient tonicity.
TonEBP
protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration. It was reported recently that long-term CsA treatment was associated with decreased renal expression of
TonEBP
target genes, including aquaporin-2, urea transporter, and aldose reductase. This study tested the hypothesis that long-term CsA treatment reduces the salinity/tonicity of the renal medullary interstitium as a result of inhibition of active sodium transporters, leading to downregulation of
TonEBP
. CsA treatment for 7 d did not affect
TonEBP
or renal function. Whereas expression of sodium transporters was altered, the medullary tonicity seemed unchanged. Conversely, 28 d of CsA treatment led to downregulation of
TonEBP
and overt nephrotoxicity. The downregulation of
TonEBP
involved reduced expression, cytoplasmic shift, and reduced transcription of its target genes. This was associated with reduced expression of active sodium transporters-sodium/potassium/chloride transporter type 2 (NKCC2), sodium/chloride transporter, and Na(+),K(+)-ATPase-along with increased sodium excretion and reduced urinary concentration. Infusion of vasopressin restored the expression of NKCC2 in the outer medulla as well as the expression and the activity of
TonEBP
. It is concluded that the downregulation of
TonEBP
in the setting of long-term CsA administration is secondary to the reduced tonicity of the renal medullary interstitium.
...
PMID:Downregulation of renal sodium transporters and tonicity-responsive enhancer binding protein by long-term treatment with cyclosporin A. 1720 15
