Thyroid transcription factor-1 facilitates cerebrospinal fluid formation by regulating aquaporin-1 synthesis in the brain.
In the brain, aquaporin-1 (AQP-1), a water channel for high osmotic water permeability, is mainly expressed in the apical membrane of the ventricular choroid plexus and regulates formation of cerebrospinal fluid (CSF). Although the physiology of AQP-1 has been the subject of several publications, much less is known about the trans-acting factors involved in the control of AQP-1 gene expression. Here we report that TTF-1, a homeodomain-containing transcriptional regulator, is coexpressed with AQP-1 in the rat brain choroid plexus and enhances AQP-1 gene transcription by binding to conserved core TTF-1-binding motifs in the 5'-flanking region of the AQP-1 gene. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased AQP-1 synthesis and reduced CSF formation. In addition, blockade of TTF-1 synthesis increased survival of the animals following acute water intoxication-induced brain edema. These results suggest that TTF-1 is physiologically involved in the transcriptional control of AQP-1, which is required for CSF formation.
Kim
Jae Geun
JG
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, South Korea.
Son
Young June
YJ
Yun
Chang Ho
CH
Kim
Young Il
YI
Nam-Goong
Il Seong
IS
Park
Jun Heon
JH
Park
Sang Kyu
SK
Ojeda
Sergio R
SR
D'Elia
Angela Valentina
AV
Damante
Giuseppe
G
Lee
Byung Ju
BJ
D000818:Animals; D051398:Aquaporin 1 / Q000096:biosynthesis* / Q000235:genetics; D001929:Brain Edema / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014869:Water Intoxication / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology
C496022:Aqp1 protein, rat; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D051398:Aquaporin 1