Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD

Rama Nadella, Joe B. Blumer, Guangfu Jia, Michelle Kwon, Talha Akbulut, Feng Qian, Filip Sedlic, Tetsuro Wakatsuki, William E. Sweeney, Patricia D. Wilson, Stephen M. Lanier, Frank Park

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The activation of heterotrimeric G protein signaling is a key feature in the pathophysiology of polycystic kidney diseases (PKD). In this study, we report abnormal overexpression of activator of G protein signaling 3 (AGS3), a receptor-independent regulator of heterotrimeric G proteins, in rodents and humans with both autosomal recessive and autosomal dominant PKD. Increased AGS3 expression correlated with kidney size, which is an index of severity of cystic kidney disease. AGS3 expression localized exclusively to distal tubular segments in both normal and cystic kidneys. Short hairpin RNA-induced knockdown of endogenous AGS3 protein significantly reduced proliferation of cystic renal epithelial cells by 26 ± 2% (P < 0.001) compared with vehicle-treated and control short hairpin RNA-expressing epithelial cells. In summary, this study suggests a relationship between aberrantly increased AGS3 expression in renal tubular epithelia affected by PKD and epithelial cell proliferation. AGS3 may play a receptor-independent role to regulate Gα subunit function and control epithelial cell function in PKD.

Original languageEnglish (US)
Pages (from-to)1275-1280
Number of pages6
JournalJournal of the American Society of Nephrology
Volume21
Issue number8
DOIs
StatePublished - Aug 1 2010

Fingerprint

Polycystic Kidney Diseases
GTP-Binding Proteins
Epithelial Cells
Cell Proliferation
Cystic Kidney Diseases
Heterotrimeric GTP-Binding Proteins
Kidney
Small Interfering RNA
Autosomal Dominant Polycystic Kidney
Rodentia
Epithelium
Proteins

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD. / Nadella, Rama; Blumer, Joe B.; Jia, Guangfu; Kwon, Michelle; Akbulut, Talha; Qian, Feng; Sedlic, Filip; Wakatsuki, Tetsuro; Sweeney, William E.; Wilson, Patricia D.; Lanier, Stephen M.; Park, Frank.

In: Journal of the American Society of Nephrology, Vol. 21, No. 8, 01.08.2010, p. 1275-1280.

Research output: Contribution to journalArticle

Nadella, R, Blumer, JB, Jia, G, Kwon, M, Akbulut, T, Qian, F, Sedlic, F, Wakatsuki, T, Sweeney, WE, Wilson, PD, Lanier, SM & Park, F 2010, 'Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD', Journal of the American Society of Nephrology, vol. 21, no. 8, pp. 1275-1280. https://doi.org/10.1681/ASN.2009121224
Nadella, Rama ; Blumer, Joe B. ; Jia, Guangfu ; Kwon, Michelle ; Akbulut, Talha ; Qian, Feng ; Sedlic, Filip ; Wakatsuki, Tetsuro ; Sweeney, William E. ; Wilson, Patricia D. ; Lanier, Stephen M. ; Park, Frank. / Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD. In: Journal of the American Society of Nephrology. 2010 ; Vol. 21, No. 8. pp. 1275-1280.
@article{484e5fc6731040acbd3aadb6965cce4c,
title = "Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD",
abstract = "The activation of heterotrimeric G protein signaling is a key feature in the pathophysiology of polycystic kidney diseases (PKD). In this study, we report abnormal overexpression of activator of G protein signaling 3 (AGS3), a receptor-independent regulator of heterotrimeric G proteins, in rodents and humans with both autosomal recessive and autosomal dominant PKD. Increased AGS3 expression correlated with kidney size, which is an index of severity of cystic kidney disease. AGS3 expression localized exclusively to distal tubular segments in both normal and cystic kidneys. Short hairpin RNA-induced knockdown of endogenous AGS3 protein significantly reduced proliferation of cystic renal epithelial cells by 26 ± 2{\%} (P < 0.001) compared with vehicle-treated and control short hairpin RNA-expressing epithelial cells. In summary, this study suggests a relationship between aberrantly increased AGS3 expression in renal tubular epithelia affected by PKD and epithelial cell proliferation. AGS3 may play a receptor-independent role to regulate Gα subunit function and control epithelial cell function in PKD.",
author = "Rama Nadella and Blumer, {Joe B.} and Guangfu Jia and Michelle Kwon and Talha Akbulut and Feng Qian and Filip Sedlic and Tetsuro Wakatsuki and Sweeney, {William E.} and Wilson, {Patricia D.} and Lanier, {Stephen M.} and Frank Park",
year = "2010",
month = "8",
day = "1",
doi = "10.1681/ASN.2009121224",
language = "English (US)",
volume = "21",
pages = "1275--1280",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "8",

}

TY - JOUR

T1 - Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD

AU - Nadella, Rama

AU - Blumer, Joe B.

AU - Jia, Guangfu

AU - Kwon, Michelle

AU - Akbulut, Talha

AU - Qian, Feng

AU - Sedlic, Filip

AU - Wakatsuki, Tetsuro

AU - Sweeney, William E.

AU - Wilson, Patricia D.

AU - Lanier, Stephen M.

AU - Park, Frank

PY - 2010/8/1

Y1 - 2010/8/1

N2 - The activation of heterotrimeric G protein signaling is a key feature in the pathophysiology of polycystic kidney diseases (PKD). In this study, we report abnormal overexpression of activator of G protein signaling 3 (AGS3), a receptor-independent regulator of heterotrimeric G proteins, in rodents and humans with both autosomal recessive and autosomal dominant PKD. Increased AGS3 expression correlated with kidney size, which is an index of severity of cystic kidney disease. AGS3 expression localized exclusively to distal tubular segments in both normal and cystic kidneys. Short hairpin RNA-induced knockdown of endogenous AGS3 protein significantly reduced proliferation of cystic renal epithelial cells by 26 ± 2% (P < 0.001) compared with vehicle-treated and control short hairpin RNA-expressing epithelial cells. In summary, this study suggests a relationship between aberrantly increased AGS3 expression in renal tubular epithelia affected by PKD and epithelial cell proliferation. AGS3 may play a receptor-independent role to regulate Gα subunit function and control epithelial cell function in PKD.

AB - The activation of heterotrimeric G protein signaling is a key feature in the pathophysiology of polycystic kidney diseases (PKD). In this study, we report abnormal overexpression of activator of G protein signaling 3 (AGS3), a receptor-independent regulator of heterotrimeric G proteins, in rodents and humans with both autosomal recessive and autosomal dominant PKD. Increased AGS3 expression correlated with kidney size, which is an index of severity of cystic kidney disease. AGS3 expression localized exclusively to distal tubular segments in both normal and cystic kidneys. Short hairpin RNA-induced knockdown of endogenous AGS3 protein significantly reduced proliferation of cystic renal epithelial cells by 26 ± 2% (P < 0.001) compared with vehicle-treated and control short hairpin RNA-expressing epithelial cells. In summary, this study suggests a relationship between aberrantly increased AGS3 expression in renal tubular epithelia affected by PKD and epithelial cell proliferation. AGS3 may play a receptor-independent role to regulate Gα subunit function and control epithelial cell function in PKD.

UR - http://www.scopus.com/inward/record.url?scp=77955651305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955651305&partnerID=8YFLogxK

U2 - 10.1681/ASN.2009121224

DO - 10.1681/ASN.2009121224

M3 - Article

VL - 21

SP - 1275

EP - 1280

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 8

ER -