Subcloning and regulation of a human intestinal sodium-phosphate cotransporter gene

Persistent Link:
http://hdl.handle.net/10150/284333
Title:
Subcloning and regulation of a human intestinal sodium-phosphate cotransporter gene
Author:
Xu, Hua
Issue Date:
2001
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Phosphate plays a critical role in the body as a constituent of bone and tooth for body development, and as a urinary buffer for pH in body acid-base balance regulation. The phosphorus level in blood in human is between 3.0 to 4.5 mg/dl. When the blood phosphate concentration is lower than 2.5 mg/dl, the person develops hypophosphatemia. When the blood phosphate concentration is higher than 4.5 mg/dl, the person develops hyperphosphatemia. It is critically important for the body to control the phosphate level in blood and maintain the phosphate homeostasis. The kidney and the intestine are the important sites to regulate phosphate homeostasis. This dissertation research was to explore the transporter gene(s) involved in the intestinal sodium-dependent phosphate absorption in human and to investigate the role of sodium-phosphate (NaPi) transporters in phosphate homeostatic regulation. The research was performed to test the hypothesis that the sodium-dependent phosphate (NaPi) cotransporter is involved in the phosphate absorption in intestine and various physiological regulators modulate the activity of this transporter. A cDNA encoding a novel human small intestinal Na⁺-P i transporter was isolated from a human intestinal cDNA library. This cDNA encodes a 689 amino acid polypeptide which is different from the renal NaPi cotransporters. This human intestinal NaPi cotransporter gene was mapped to human chromosome 4p15.1--p15.3 by the F̲luorescence I̲n-S̲itu H̲y̲bridization (FISH) method. The human intestinal NaPi cotransporter gene structure was studied by screening a human genomic DNA library. This gene contains 12 exons and 11 introns. There were two transcription initiation sites identified by primer extension. In vivo and in vitro studies showed that the intestinal NaPi cotransporter gene expression is regulated by EGF and vitamin D3. EGF inhibits NaPi-cotransporter gene expression, while vitamin D3 stimulates NaPi-cotransporter gene expression. From these studies, I concluded that the intestinal sodium-dependent phosphate absorption is mainly mediated by intestinal NaPi cotransporters (NaPi-IIb), and this transporter is modulated by various physiological regulators in order to maintain the phosphate homeostasis.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Molecular.; Health Sciences, Nutrition.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Ghishan, Fayez K.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleSubcloning and regulation of a human intestinal sodium-phosphate cotransporter geneen_US
dc.creatorXu, Huaen_US
dc.contributor.authorXu, Huaen_US
dc.date.issued2001en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractPhosphate plays a critical role in the body as a constituent of bone and tooth for body development, and as a urinary buffer for pH in body acid-base balance regulation. The phosphorus level in blood in human is between 3.0 to 4.5 mg/dl. When the blood phosphate concentration is lower than 2.5 mg/dl, the person develops hypophosphatemia. When the blood phosphate concentration is higher than 4.5 mg/dl, the person develops hyperphosphatemia. It is critically important for the body to control the phosphate level in blood and maintain the phosphate homeostasis. The kidney and the intestine are the important sites to regulate phosphate homeostasis. This dissertation research was to explore the transporter gene(s) involved in the intestinal sodium-dependent phosphate absorption in human and to investigate the role of sodium-phosphate (NaPi) transporters in phosphate homeostatic regulation. The research was performed to test the hypothesis that the sodium-dependent phosphate (NaPi) cotransporter is involved in the phosphate absorption in intestine and various physiological regulators modulate the activity of this transporter. A cDNA encoding a novel human small intestinal Na⁺-P i transporter was isolated from a human intestinal cDNA library. This cDNA encodes a 689 amino acid polypeptide which is different from the renal NaPi cotransporters. This human intestinal NaPi cotransporter gene was mapped to human chromosome 4p15.1--p15.3 by the F̲luorescence I̲n-S̲itu H̲y̲bridization (FISH) method. The human intestinal NaPi cotransporter gene structure was studied by screening a human genomic DNA library. This gene contains 12 exons and 11 introns. There were two transcription initiation sites identified by primer extension. In vivo and in vitro studies showed that the intestinal NaPi cotransporter gene expression is regulated by EGF and vitamin D3. EGF inhibits NaPi-cotransporter gene expression, while vitamin D3 stimulates NaPi-cotransporter gene expression. From these studies, I concluded that the intestinal sodium-dependent phosphate absorption is mainly mediated by intestinal NaPi cotransporters (NaPi-IIb), and this transporter is modulated by various physiological regulators in order to maintain the phosphate homeostasis.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Molecular.en_US
dc.subjectHealth Sciences, Nutrition.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorGhishan, Fayez K.en_US
dc.identifier.proquest3031411en_US
dc.identifier.bibrecord.b42289233en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.