Development of a novel transgenic rat overexpressing the P2Y2 nucleotide receptor using a lentiviral vector

Cansu Agca, Cheikh Seye, Corinna M. Kashuba Benson, Shivaji Rikka, Anthony W S Chan, Gary A. Weisman, Yuksel Agca

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The G protein-coupled P2Y2 nucleotide receptor (P2Y 2R) is upregulated in response to stress and tissue injury and has been postulated to play a role in chronic inflammation seen in atherosclerosis, Alzheimer's disease and Sjögren's syndrome. The role of P2Y2R upregulation in vivo is poorly understood, in part due to the lack of a P2Y 2R overexpressing animal model. The P2Y2R overexpressing transgenic rat was generated using a lentiviral vector. Rats overexpressing P2Y2R showed a significant increase in P2Y2R mRNA levels in all tissues screened as compared to nontransgenic rats. Fura 2 imaging of smooth muscle cells (SMCs) isolated from aorta indicated that the percentage of cells exhibiting increases in the intracellular free calcium concentration in response to P2Y2R agonists was significantly greater in freshly isolated SMCs from transgenic rats than wild-type controls. Histopathological examination of tissues revealed that P2Y2R overexpressing rats develop lymphocytic infiltration in lacrimal glands and kidneys as early as at 3 months of age. These rats show similarities to patients with Sjögren's syndrome who display lymphocyte-mediated tissue damage. This transgenic rat model of P2Y2R overexpression may prove useful for linking P2Y 2R upregulation with chronic inflammatory diseases, neurodegenerative diseases and Sjögren's syndrome.

Original languageEnglish (US)
Pages (from-to)447-458
Number of pages12
JournalJournal of Vascular Research
Volume46
Issue number5
DOIs
StatePublished - Aug 2009
Externally publishedYes

Fingerprint

Purinergic P2Y2 Receptors
Transgenic Rats
Nucleotides
Smooth Muscle Myocytes
Up-Regulation
Lacrimal Apparatus
Fura-2
GTP-Binding Proteins
Neurodegenerative Diseases
Aorta
Atherosclerosis
Alzheimer Disease
Chronic Disease
Animal Models
Lymphocytes
Inflammation
Calcium
Kidney
Messenger RNA
Wounds and Injuries

Keywords

  • Nucleotide
  • P2Y receptor
  • Sjögren's syndrome, transgenic rat

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Development of a novel transgenic rat overexpressing the P2Y2 nucleotide receptor using a lentiviral vector. / Agca, Cansu; Seye, Cheikh; Kashuba Benson, Corinna M.; Rikka, Shivaji; Chan, Anthony W S; Weisman, Gary A.; Agca, Yuksel.

In: Journal of Vascular Research, Vol. 46, No. 5, 08.2009, p. 447-458.

Research output: Contribution to journalArticle

Agca, Cansu ; Seye, Cheikh ; Kashuba Benson, Corinna M. ; Rikka, Shivaji ; Chan, Anthony W S ; Weisman, Gary A. ; Agca, Yuksel. / Development of a novel transgenic rat overexpressing the P2Y2 nucleotide receptor using a lentiviral vector. In: Journal of Vascular Research. 2009 ; Vol. 46, No. 5. pp. 447-458.
@article{8d7284c5932c4f0cb3924b967bafd477,
title = "Development of a novel transgenic rat overexpressing the P2Y2 nucleotide receptor using a lentiviral vector",
abstract = "The G protein-coupled P2Y2 nucleotide receptor (P2Y 2R) is upregulated in response to stress and tissue injury and has been postulated to play a role in chronic inflammation seen in atherosclerosis, Alzheimer's disease and Sj{\"o}gren's syndrome. The role of P2Y2R upregulation in vivo is poorly understood, in part due to the lack of a P2Y 2R overexpressing animal model. The P2Y2R overexpressing transgenic rat was generated using a lentiviral vector. Rats overexpressing P2Y2R showed a significant increase in P2Y2R mRNA levels in all tissues screened as compared to nontransgenic rats. Fura 2 imaging of smooth muscle cells (SMCs) isolated from aorta indicated that the percentage of cells exhibiting increases in the intracellular free calcium concentration in response to P2Y2R agonists was significantly greater in freshly isolated SMCs from transgenic rats than wild-type controls. Histopathological examination of tissues revealed that P2Y2R overexpressing rats develop lymphocytic infiltration in lacrimal glands and kidneys as early as at 3 months of age. These rats show similarities to patients with Sj{\"o}gren's syndrome who display lymphocyte-mediated tissue damage. This transgenic rat model of P2Y2R overexpression may prove useful for linking P2Y 2R upregulation with chronic inflammatory diseases, neurodegenerative diseases and Sj{\"o}gren's syndrome.",
keywords = "Nucleotide, P2Y receptor, Sj{\"o}gren's syndrome, transgenic rat",
author = "Cansu Agca and Cheikh Seye and {Kashuba Benson}, {Corinna M.} and Shivaji Rikka and Chan, {Anthony W S} and Weisman, {Gary A.} and Yuksel Agca",
year = "2009",
month = "8",
doi = "10.1159/000194274",
language = "English (US)",
volume = "46",
pages = "447--458",
journal = "Journal of Vascular Research",
issn = "1018-1172",
publisher = "S. Karger AG",
number = "5",

}

TY - JOUR

T1 - Development of a novel transgenic rat overexpressing the P2Y2 nucleotide receptor using a lentiviral vector

AU - Agca, Cansu

AU - Seye, Cheikh

AU - Kashuba Benson, Corinna M.

AU - Rikka, Shivaji

AU - Chan, Anthony W S

AU - Weisman, Gary A.

AU - Agca, Yuksel

PY - 2009/8

Y1 - 2009/8

N2 - The G protein-coupled P2Y2 nucleotide receptor (P2Y 2R) is upregulated in response to stress and tissue injury and has been postulated to play a role in chronic inflammation seen in atherosclerosis, Alzheimer's disease and Sjögren's syndrome. The role of P2Y2R upregulation in vivo is poorly understood, in part due to the lack of a P2Y 2R overexpressing animal model. The P2Y2R overexpressing transgenic rat was generated using a lentiviral vector. Rats overexpressing P2Y2R showed a significant increase in P2Y2R mRNA levels in all tissues screened as compared to nontransgenic rats. Fura 2 imaging of smooth muscle cells (SMCs) isolated from aorta indicated that the percentage of cells exhibiting increases in the intracellular free calcium concentration in response to P2Y2R agonists was significantly greater in freshly isolated SMCs from transgenic rats than wild-type controls. Histopathological examination of tissues revealed that P2Y2R overexpressing rats develop lymphocytic infiltration in lacrimal glands and kidneys as early as at 3 months of age. These rats show similarities to patients with Sjögren's syndrome who display lymphocyte-mediated tissue damage. This transgenic rat model of P2Y2R overexpression may prove useful for linking P2Y 2R upregulation with chronic inflammatory diseases, neurodegenerative diseases and Sjögren's syndrome.

AB - The G protein-coupled P2Y2 nucleotide receptor (P2Y 2R) is upregulated in response to stress and tissue injury and has been postulated to play a role in chronic inflammation seen in atherosclerosis, Alzheimer's disease and Sjögren's syndrome. The role of P2Y2R upregulation in vivo is poorly understood, in part due to the lack of a P2Y 2R overexpressing animal model. The P2Y2R overexpressing transgenic rat was generated using a lentiviral vector. Rats overexpressing P2Y2R showed a significant increase in P2Y2R mRNA levels in all tissues screened as compared to nontransgenic rats. Fura 2 imaging of smooth muscle cells (SMCs) isolated from aorta indicated that the percentage of cells exhibiting increases in the intracellular free calcium concentration in response to P2Y2R agonists was significantly greater in freshly isolated SMCs from transgenic rats than wild-type controls. Histopathological examination of tissues revealed that P2Y2R overexpressing rats develop lymphocytic infiltration in lacrimal glands and kidneys as early as at 3 months of age. These rats show similarities to patients with Sjögren's syndrome who display lymphocyte-mediated tissue damage. This transgenic rat model of P2Y2R overexpression may prove useful for linking P2Y 2R upregulation with chronic inflammatory diseases, neurodegenerative diseases and Sjögren's syndrome.

KW - Nucleotide

KW - P2Y receptor

KW - Sjögren's syndrome, transgenic rat

UR - http://www.scopus.com/inward/record.url?scp=58249130841&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58249130841&partnerID=8YFLogxK

U2 - 10.1159/000194274

DO - 10.1159/000194274

M3 - Article

C2 - 19155635

AN - SCOPUS:58249130841

VL - 46

SP - 447

EP - 458

JO - Journal of Vascular Research

JF - Journal of Vascular Research

SN - 1018-1172

IS - 5

ER -