Netrin-1 overexpression protects kidney from ischemia reperfusion injury by suppressing apoptosis

Weiwei Wang, William Brian Reeves, Laurent Pays, Patrick Mehlen, Ganesan Ramesh

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Netrin-1, a diffusible laminin-related protein, is highly expressed in the kidney. However, the pathophysiological roles of netrin-1 in the kidney are unknown. To address this question directly, we used transgenic mice that overexpress chicken netrin-1 in the kidney. Netrin-1 overexpression was confirmed by real-time RT-PCR and Western blot analysis. Eight-week-old wild-type and transgenic mice were subjected to 26 minutes of renal ischemia followed by reperfusion for 72 hours. Wild-type mice developed more severe renal dysfunction by 24 hours than netrin-1 transgenic mice. Functional improvement was associated with better preservation of morphology, reduced cytokine expression, and reduced oxidative stress in the kidney of transgenic mice as compared with wild-type mice. In addition, both basal and reperfusion-induced cell proliferation were dramatically increased in transgenic kidneys as determined by Ki-67 staining. Interestingly, ischemia reperfusion induced a large increase in apoptosis in wild-type mice but not in netrin-1 transgenic mice that was associated with reduced caspase-3 activation in the transgenic kidney. These results suggest that netrin-1 protects renal tubular epithelial cells against ischemia reperfusion-induced injury by increasing proliferation and suppressing apoptosis.

Original languageEnglish (US)
Pages (from-to)1010-1018
Number of pages9
JournalAmerican Journal of Pathology
Volume175
Issue number3
DOIs
StatePublished - Sep 1 2009

Fingerprint

Reperfusion Injury
Apoptosis
Kidney
Transgenic Mice
Reperfusion
Ischemia
netrin-1
Laminin
Caspase 3
Real-Time Polymerase Chain Reaction
Chickens
Oxidative Stress
Western Blotting
Epithelial Cells
Cell Proliferation
Staining and Labeling
Cytokines

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Netrin-1 overexpression protects kidney from ischemia reperfusion injury by suppressing apoptosis. / Wang, Weiwei; Reeves, William Brian; Pays, Laurent; Mehlen, Patrick; Ramesh, Ganesan.

In: American Journal of Pathology, Vol. 175, No. 3, 01.09.2009, p. 1010-1018.

Research output: Contribution to journalArticle

Wang, Weiwei ; Reeves, William Brian ; Pays, Laurent ; Mehlen, Patrick ; Ramesh, Ganesan. / Netrin-1 overexpression protects kidney from ischemia reperfusion injury by suppressing apoptosis. In: American Journal of Pathology. 2009 ; Vol. 175, No. 3. pp. 1010-1018.
@article{118cf5cace774d71b83c339e67f373c9,
title = "Netrin-1 overexpression protects kidney from ischemia reperfusion injury by suppressing apoptosis",
abstract = "Netrin-1, a diffusible laminin-related protein, is highly expressed in the kidney. However, the pathophysiological roles of netrin-1 in the kidney are unknown. To address this question directly, we used transgenic mice that overexpress chicken netrin-1 in the kidney. Netrin-1 overexpression was confirmed by real-time RT-PCR and Western blot analysis. Eight-week-old wild-type and transgenic mice were subjected to 26 minutes of renal ischemia followed by reperfusion for 72 hours. Wild-type mice developed more severe renal dysfunction by 24 hours than netrin-1 transgenic mice. Functional improvement was associated with better preservation of morphology, reduced cytokine expression, and reduced oxidative stress in the kidney of transgenic mice as compared with wild-type mice. In addition, both basal and reperfusion-induced cell proliferation were dramatically increased in transgenic kidneys as determined by Ki-67 staining. Interestingly, ischemia reperfusion induced a large increase in apoptosis in wild-type mice but not in netrin-1 transgenic mice that was associated with reduced caspase-3 activation in the transgenic kidney. These results suggest that netrin-1 protects renal tubular epithelial cells against ischemia reperfusion-induced injury by increasing proliferation and suppressing apoptosis.",
author = "Weiwei Wang and Reeves, {William Brian} and Laurent Pays and Patrick Mehlen and Ganesan Ramesh",
year = "2009",
month = "9",
day = "1",
doi = "10.2353/ajpath.2009.090224",
language = "English (US)",
volume = "175",
pages = "1010--1018",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Netrin-1 overexpression protects kidney from ischemia reperfusion injury by suppressing apoptosis

AU - Wang, Weiwei

AU - Reeves, William Brian

AU - Pays, Laurent

AU - Mehlen, Patrick

AU - Ramesh, Ganesan

PY - 2009/9/1

Y1 - 2009/9/1

N2 - Netrin-1, a diffusible laminin-related protein, is highly expressed in the kidney. However, the pathophysiological roles of netrin-1 in the kidney are unknown. To address this question directly, we used transgenic mice that overexpress chicken netrin-1 in the kidney. Netrin-1 overexpression was confirmed by real-time RT-PCR and Western blot analysis. Eight-week-old wild-type and transgenic mice were subjected to 26 minutes of renal ischemia followed by reperfusion for 72 hours. Wild-type mice developed more severe renal dysfunction by 24 hours than netrin-1 transgenic mice. Functional improvement was associated with better preservation of morphology, reduced cytokine expression, and reduced oxidative stress in the kidney of transgenic mice as compared with wild-type mice. In addition, both basal and reperfusion-induced cell proliferation were dramatically increased in transgenic kidneys as determined by Ki-67 staining. Interestingly, ischemia reperfusion induced a large increase in apoptosis in wild-type mice but not in netrin-1 transgenic mice that was associated with reduced caspase-3 activation in the transgenic kidney. These results suggest that netrin-1 protects renal tubular epithelial cells against ischemia reperfusion-induced injury by increasing proliferation and suppressing apoptosis.

AB - Netrin-1, a diffusible laminin-related protein, is highly expressed in the kidney. However, the pathophysiological roles of netrin-1 in the kidney are unknown. To address this question directly, we used transgenic mice that overexpress chicken netrin-1 in the kidney. Netrin-1 overexpression was confirmed by real-time RT-PCR and Western blot analysis. Eight-week-old wild-type and transgenic mice were subjected to 26 minutes of renal ischemia followed by reperfusion for 72 hours. Wild-type mice developed more severe renal dysfunction by 24 hours than netrin-1 transgenic mice. Functional improvement was associated with better preservation of morphology, reduced cytokine expression, and reduced oxidative stress in the kidney of transgenic mice as compared with wild-type mice. In addition, both basal and reperfusion-induced cell proliferation were dramatically increased in transgenic kidneys as determined by Ki-67 staining. Interestingly, ischemia reperfusion induced a large increase in apoptosis in wild-type mice but not in netrin-1 transgenic mice that was associated with reduced caspase-3 activation in the transgenic kidney. These results suggest that netrin-1 protects renal tubular epithelial cells against ischemia reperfusion-induced injury by increasing proliferation and suppressing apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=70349243195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349243195&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2009.090224

DO - 10.2353/ajpath.2009.090224

M3 - Article

VL - 175

SP - 1010

EP - 1018

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -