Pax transactivation-domain interacting protein is required for urine concentration and osmotolerance in collecting duct epithelia

Doyeob Kim, Min Wang, Qi Cai, Heddwen L Brooks, Gregory R. Dressler

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Pax transactivation-domain interacting protein (PTIP) is a widely expressed nuclear protein that is essential for early embryonic development. PTIP was first identified on the basis of its interactions with the developmental regulator Pax2 but can also bind to other nuclear transcription factors. The Pax2 protein is essential for development of the renal epithelia and for regulating the response of mature collecting ducts to hyperosmotic stress. For determination of whether PTIP also functions in more differentiated cell types, the Cre-LoxP system was used to delete the ptip gene in the renal collecting ducts using Ksp-Cre driver mice. Collecting duct-specific ptip knockout mice were viable with little discernible phenotype under normal physiologic conditions. However, collecting duct-specific ptip mutants were unable to concentrate urine after the treatment of desamino-cis, D-arginine vasopressin, an antidiuretic hormone. Furthermore, aquaporin-2 (AQP2) expression in the inner medulla of the ptip knockout mice was decreased approximately 10-fold compared with that of wild-type littermates. Expression level of tonicity responsive enhancer binding protein, a transcription factor of AQP2, is not altered in the mutant mice, but its nuclear localization in the inner medulla is unresponsive after treatment with vasopressin agonists. This was due, at least in part, to decreased expression of the arginine vasopressin receptor 2 in ptip mutants. Furthermore, ptip null inner medullary collecting duct cells were sensitive to hyperosmolality in vitro. Thus, ptip is required for the urine concentration mechanism by modulating arginine vasopressin receptor 2 and AQP2 expression in the inner medulla. The data suggest an essential role for ptip in regulating urine concentration and in controlling survival of collecting duct epithelial cells in high osmolality.

Original languageEnglish (US)
Pages (from-to)1458-1465
Number of pages8
JournalJournal of the American Society of Nephrology
Volume18
Issue number5
DOIs
StatePublished - May 2007

Fingerprint

Aquaporin 2
Transcriptional Activation
Vasopressin Receptors
Epithelium
Urine
Vasopressins
Knockout Mice
Transcription Factors
NFATC Transcription Factors
Kidney
Arginine Vasopressin
Nuclear Proteins
Osmolar Concentration
Embryonic Development
Epithelial Cells
Phenotype
Genes
Protein Domains
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

Pax transactivation-domain interacting protein is required for urine concentration and osmotolerance in collecting duct epithelia. / Kim, Doyeob; Wang, Min; Cai, Qi; Brooks, Heddwen L; Dressler, Gregory R.

In: Journal of the American Society of Nephrology, Vol. 18, No. 5, 05.2007, p. 1458-1465.

Research output: Contribution to journalArticle

@article{2e9701099b1f41e09e208f5cc62460ad,
title = "Pax transactivation-domain interacting protein is required for urine concentration and osmotolerance in collecting duct epithelia",
abstract = "Pax transactivation-domain interacting protein (PTIP) is a widely expressed nuclear protein that is essential for early embryonic development. PTIP was first identified on the basis of its interactions with the developmental regulator Pax2 but can also bind to other nuclear transcription factors. The Pax2 protein is essential for development of the renal epithelia and for regulating the response of mature collecting ducts to hyperosmotic stress. For determination of whether PTIP also functions in more differentiated cell types, the Cre-LoxP system was used to delete the ptip gene in the renal collecting ducts using Ksp-Cre driver mice. Collecting duct-specific ptip knockout mice were viable with little discernible phenotype under normal physiologic conditions. However, collecting duct-specific ptip mutants were unable to concentrate urine after the treatment of desamino-cis, D-arginine vasopressin, an antidiuretic hormone. Furthermore, aquaporin-2 (AQP2) expression in the inner medulla of the ptip knockout mice was decreased approximately 10-fold compared with that of wild-type littermates. Expression level of tonicity responsive enhancer binding protein, a transcription factor of AQP2, is not altered in the mutant mice, but its nuclear localization in the inner medulla is unresponsive after treatment with vasopressin agonists. This was due, at least in part, to decreased expression of the arginine vasopressin receptor 2 in ptip mutants. Furthermore, ptip null inner medullary collecting duct cells were sensitive to hyperosmolality in vitro. Thus, ptip is required for the urine concentration mechanism by modulating arginine vasopressin receptor 2 and AQP2 expression in the inner medulla. The data suggest an essential role for ptip in regulating urine concentration and in controlling survival of collecting duct epithelial cells in high osmolality.",
author = "Doyeob Kim and Min Wang and Qi Cai and Brooks, {Heddwen L} and Dressler, {Gregory R.}",
year = "2007",
month = "5",
doi = "10.1681/ASN.2006060625",
language = "English (US)",
volume = "18",
pages = "1458--1465",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "5",

}

TY - JOUR

T1 - Pax transactivation-domain interacting protein is required for urine concentration and osmotolerance in collecting duct epithelia

AU - Kim, Doyeob

AU - Wang, Min

AU - Cai, Qi

AU - Brooks, Heddwen L

AU - Dressler, Gregory R.

PY - 2007/5

Y1 - 2007/5

N2 - Pax transactivation-domain interacting protein (PTIP) is a widely expressed nuclear protein that is essential for early embryonic development. PTIP was first identified on the basis of its interactions with the developmental regulator Pax2 but can also bind to other nuclear transcription factors. The Pax2 protein is essential for development of the renal epithelia and for regulating the response of mature collecting ducts to hyperosmotic stress. For determination of whether PTIP also functions in more differentiated cell types, the Cre-LoxP system was used to delete the ptip gene in the renal collecting ducts using Ksp-Cre driver mice. Collecting duct-specific ptip knockout mice were viable with little discernible phenotype under normal physiologic conditions. However, collecting duct-specific ptip mutants were unable to concentrate urine after the treatment of desamino-cis, D-arginine vasopressin, an antidiuretic hormone. Furthermore, aquaporin-2 (AQP2) expression in the inner medulla of the ptip knockout mice was decreased approximately 10-fold compared with that of wild-type littermates. Expression level of tonicity responsive enhancer binding protein, a transcription factor of AQP2, is not altered in the mutant mice, but its nuclear localization in the inner medulla is unresponsive after treatment with vasopressin agonists. This was due, at least in part, to decreased expression of the arginine vasopressin receptor 2 in ptip mutants. Furthermore, ptip null inner medullary collecting duct cells were sensitive to hyperosmolality in vitro. Thus, ptip is required for the urine concentration mechanism by modulating arginine vasopressin receptor 2 and AQP2 expression in the inner medulla. The data suggest an essential role for ptip in regulating urine concentration and in controlling survival of collecting duct epithelial cells in high osmolality.

AB - Pax transactivation-domain interacting protein (PTIP) is a widely expressed nuclear protein that is essential for early embryonic development. PTIP was first identified on the basis of its interactions with the developmental regulator Pax2 but can also bind to other nuclear transcription factors. The Pax2 protein is essential for development of the renal epithelia and for regulating the response of mature collecting ducts to hyperosmotic stress. For determination of whether PTIP also functions in more differentiated cell types, the Cre-LoxP system was used to delete the ptip gene in the renal collecting ducts using Ksp-Cre driver mice. Collecting duct-specific ptip knockout mice were viable with little discernible phenotype under normal physiologic conditions. However, collecting duct-specific ptip mutants were unable to concentrate urine after the treatment of desamino-cis, D-arginine vasopressin, an antidiuretic hormone. Furthermore, aquaporin-2 (AQP2) expression in the inner medulla of the ptip knockout mice was decreased approximately 10-fold compared with that of wild-type littermates. Expression level of tonicity responsive enhancer binding protein, a transcription factor of AQP2, is not altered in the mutant mice, but its nuclear localization in the inner medulla is unresponsive after treatment with vasopressin agonists. This was due, at least in part, to decreased expression of the arginine vasopressin receptor 2 in ptip mutants. Furthermore, ptip null inner medullary collecting duct cells were sensitive to hyperosmolality in vitro. Thus, ptip is required for the urine concentration mechanism by modulating arginine vasopressin receptor 2 and AQP2 expression in the inner medulla. The data suggest an essential role for ptip in regulating urine concentration and in controlling survival of collecting duct epithelial cells in high osmolality.

UR - http://www.scopus.com/inward/record.url?scp=34248224882&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248224882&partnerID=8YFLogxK

U2 - 10.1681/ASN.2006060625

DO - 10.1681/ASN.2006060625

M3 - Article

C2 - 17429055

AN - SCOPUS:34248224882

VL - 18

SP - 1458

EP - 1465

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 5

ER -