Disruption of guanylyl cyclase-G protects against acute renal injury

Heng Lin, Ching Feng Cheng, Hsin Han Hou, Wei Shiung Lian, Ying Chi Chao, Yi Yun Ciou, Bambang Djoko, Ming Tzu Tsai, Chien Jui Cheng, Ruey Bing Yang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G-/- mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G-/- mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-κB were lower in GC-G -/- mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G-/- mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

Original languageEnglish
Pages (from-to)339-348
Number of pages10
JournalJournal of the American Society of Nephrology
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2008
Externally publishedYes

Fingerprint

Guanylate Cyclase
Acute Kidney Injury
Reperfusion Injury
Kidney
Messenger RNA
P-Selectin
Cell Surface Receptors
Second Messenger Systems
GTP-Binding Proteins
Caspase 3
Peroxidase
Reperfusion
Urea
Interleukin-6
Creatinine
Protein Isoforms
Neutrophils
Plasmids
Ischemia
Epithelial Cells

ASJC Scopus subject areas

  • Nephrology

Cite this

Lin, H., Cheng, C. F., Hou, H. H., Lian, W. S., Chao, Y. C., Ciou, Y. Y., ... Yang, R. B. (2008). Disruption of guanylyl cyclase-G protects against acute renal injury. Journal of the American Society of Nephrology, 19(2), 339-348. https://doi.org/10.1681/ASN.2007050550

Disruption of guanylyl cyclase-G protects against acute renal injury. / Lin, Heng; Cheng, Ching Feng; Hou, Hsin Han; Lian, Wei Shiung; Chao, Ying Chi; Ciou, Yi Yun; Djoko, Bambang; Tsai, Ming Tzu; Cheng, Chien Jui; Yang, Ruey Bing.

In: Journal of the American Society of Nephrology, Vol. 19, No. 2, 02.2008, p. 339-348.

Research output: Contribution to journalArticle

Lin, H, Cheng, CF, Hou, HH, Lian, WS, Chao, YC, Ciou, YY, Djoko, B, Tsai, MT, Cheng, CJ & Yang, RB 2008, 'Disruption of guanylyl cyclase-G protects against acute renal injury', Journal of the American Society of Nephrology, vol. 19, no. 2, pp. 339-348. https://doi.org/10.1681/ASN.2007050550
Lin, Heng ; Cheng, Ching Feng ; Hou, Hsin Han ; Lian, Wei Shiung ; Chao, Ying Chi ; Ciou, Yi Yun ; Djoko, Bambang ; Tsai, Ming Tzu ; Cheng, Chien Jui ; Yang, Ruey Bing. / Disruption of guanylyl cyclase-G protects against acute renal injury. In: Journal of the American Society of Nephrology. 2008 ; Vol. 19, No. 2. pp. 339-348.
@article{525989014beb4db5ba327ee441def543,
title = "Disruption of guanylyl cyclase-G protects against acute renal injury",
abstract = "The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G-/- mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G-/- mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-κB were lower in GC-G -/- mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G-/- mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.",
author = "Heng Lin and Cheng, {Ching Feng} and Hou, {Hsin Han} and Lian, {Wei Shiung} and Chao, {Ying Chi} and Ciou, {Yi Yun} and Bambang Djoko and Tsai, {Ming Tzu} and Cheng, {Chien Jui} and Yang, {Ruey Bing}",
year = "2008",
month = "2",
doi = "10.1681/ASN.2007050550",
language = "English",
volume = "19",
pages = "339--348",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "2",

}

TY - JOUR

T1 - Disruption of guanylyl cyclase-G protects against acute renal injury

AU - Lin, Heng

AU - Cheng, Ching Feng

AU - Hou, Hsin Han

AU - Lian, Wei Shiung

AU - Chao, Ying Chi

AU - Ciou, Yi Yun

AU - Djoko, Bambang

AU - Tsai, Ming Tzu

AU - Cheng, Chien Jui

AU - Yang, Ruey Bing

PY - 2008/2

Y1 - 2008/2

N2 - The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G-/- mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G-/- mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-κB were lower in GC-G -/- mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G-/- mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

AB - The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G-/- mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G-/- mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-κB were lower in GC-G -/- mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G-/- mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

UR - http://www.scopus.com/inward/record.url?scp=39049104778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39049104778&partnerID=8YFLogxK

U2 - 10.1681/ASN.2007050550

DO - 10.1681/ASN.2007050550

M3 - Article

C2 - 18199799

AN - SCOPUS:39049104778

VL - 19

SP - 339

EP - 348

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 2

ER -