Heparin-binding epidermal growth factor-like growth factor downregulates expression of activator protein-1 transcription factor after intestinal ischemia-reperfusion injury

Chih Cheng Luo, Yung Ching Ming, Hsun Chin Chao, Shih Ming Chu, See Tong Pang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury have been considered to be major contributing factors. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R injury. Recent studies have revealed that activator protein 1 (AP-1) family proteins including c-Fos and c-Jun potentially induce either the proliferation or apoptosis of the cells in the brain, heart, kidney, and liver. c-Fos and c-Jun expression has also been reported to be upregulated in postischemic intestinal epithelial cells (IECs). Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a potent cytoprotective factor in various pathologic conditions and plays a pivotal role in mediating the earliest cellular responses to injury. This study aims to examine whether HB-EGF, a proven intestinal cytoprotective molecule, exerts its protective effects through modulation of AP-1 transcription factor after intestinal I/R injury. Thirty rats were randomly divided into the following 5 groups: (1) normal control group; (2) ischemia group; (3) I/R group; (4) ischemia group with HB-EGF (400 μg/kg), and (5) I/R group with HG-EGF (400 μg/kg). c-Fos and c-Jun messenger RNAs and protein levels were determined by real-time quantitative polymerase chain reaction (PCR) and Western analyses, respectively. Statistical analysis was performed using ANOVA with Dunn's test. The messenger RNA levels of the c-Fos and c-Jun increased after intestinal ischemia or the intestinal reperfusion phase. HB-EGF pretreatment significantly decreased c-Fos and c-Jun messenger RNAs. The expression of protein levels of c-Fos and c-Jun were correlation with the expression of messenger RNA level. HB-EGF intestinal cytoprotection is mediated, in part, by downregulation of the expression of AP-1 transcription factor after intestinal I/R injury.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalNeonatology
Volume99
Issue number4
DOIs
Publication statusPublished - Jun 2011
Externally publishedYes

Fingerprint

Transcription Factor AP-1
Reperfusion Injury
Epidermal Growth Factor
Heparin
Intercellular Signaling Peptides and Proteins
Transcription Factors
Down-Regulation
Ischemia
Proto-Oncogene Proteins c-fos
Reperfusion
Messenger RNA
Apoptosis
Necrotizing Enterocolitis
Cytoprotection
Real-Time Polymerase Chain Reaction
Analysis of Variance
Cell Death
Epithelial Cells
Kidney
Control Groups

Keywords

  • Activator protein-1 transcription factor
  • c-Fos
  • c-Jun
  • Heparin-binding epidermal growth factor-like growth factor
  • Ischemia-reperfusion injury
  • Small intestine

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health

Cite this

Heparin-binding epidermal growth factor-like growth factor downregulates expression of activator protein-1 transcription factor after intestinal ischemia-reperfusion injury. / Luo, Chih Cheng; Ming, Yung Ching; Chao, Hsun Chin; Chu, Shih Ming; Pang, See Tong.

In: Neonatology, Vol. 99, No. 4, 06.2011, p. 241-246.

Research output: Contribution to journalArticle

Luo, Chih Cheng ; Ming, Yung Ching ; Chao, Hsun Chin ; Chu, Shih Ming ; Pang, See Tong. / Heparin-binding epidermal growth factor-like growth factor downregulates expression of activator protein-1 transcription factor after intestinal ischemia-reperfusion injury. In: Neonatology. 2011 ; Vol. 99, No. 4. pp. 241-246.
@article{4c26fe00c4814d3b87191608f3663dd9,
title = "Heparin-binding epidermal growth factor-like growth factor downregulates expression of activator protein-1 transcription factor after intestinal ischemia-reperfusion injury",
abstract = "The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury have been considered to be major contributing factors. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R injury. Recent studies have revealed that activator protein 1 (AP-1) family proteins including c-Fos and c-Jun potentially induce either the proliferation or apoptosis of the cells in the brain, heart, kidney, and liver. c-Fos and c-Jun expression has also been reported to be upregulated in postischemic intestinal epithelial cells (IECs). Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a potent cytoprotective factor in various pathologic conditions and plays a pivotal role in mediating the earliest cellular responses to injury. This study aims to examine whether HB-EGF, a proven intestinal cytoprotective molecule, exerts its protective effects through modulation of AP-1 transcription factor after intestinal I/R injury. Thirty rats were randomly divided into the following 5 groups: (1) normal control group; (2) ischemia group; (3) I/R group; (4) ischemia group with HB-EGF (400 μg/kg), and (5) I/R group with HG-EGF (400 μg/kg). c-Fos and c-Jun messenger RNAs and protein levels were determined by real-time quantitative polymerase chain reaction (PCR) and Western analyses, respectively. Statistical analysis was performed using ANOVA with Dunn's test. The messenger RNA levels of the c-Fos and c-Jun increased after intestinal ischemia or the intestinal reperfusion phase. HB-EGF pretreatment significantly decreased c-Fos and c-Jun messenger RNAs. The expression of protein levels of c-Fos and c-Jun were correlation with the expression of messenger RNA level. HB-EGF intestinal cytoprotection is mediated, in part, by downregulation of the expression of AP-1 transcription factor after intestinal I/R injury.",
keywords = "Activator protein-1 transcription factor, c-Fos, c-Jun, Heparin-binding epidermal growth factor-like growth factor, Ischemia-reperfusion injury, Small intestine",
author = "Luo, {Chih Cheng} and Ming, {Yung Ching} and Chao, {Hsun Chin} and Chu, {Shih Ming} and Pang, {See Tong}",
year = "2011",
month = "6",
doi = "10.1159/000318142",
language = "English",
volume = "99",
pages = "241--246",
journal = "Neonatology",
issn = "1661-7800",
publisher = "S. Karger AG",
number = "4",

}

TY - JOUR

T1 - Heparin-binding epidermal growth factor-like growth factor downregulates expression of activator protein-1 transcription factor after intestinal ischemia-reperfusion injury

AU - Luo, Chih Cheng

AU - Ming, Yung Ching

AU - Chao, Hsun Chin

AU - Chu, Shih Ming

AU - Pang, See Tong

PY - 2011/6

Y1 - 2011/6

N2 - The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury have been considered to be major contributing factors. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R injury. Recent studies have revealed that activator protein 1 (AP-1) family proteins including c-Fos and c-Jun potentially induce either the proliferation or apoptosis of the cells in the brain, heart, kidney, and liver. c-Fos and c-Jun expression has also been reported to be upregulated in postischemic intestinal epithelial cells (IECs). Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a potent cytoprotective factor in various pathologic conditions and plays a pivotal role in mediating the earliest cellular responses to injury. This study aims to examine whether HB-EGF, a proven intestinal cytoprotective molecule, exerts its protective effects through modulation of AP-1 transcription factor after intestinal I/R injury. Thirty rats were randomly divided into the following 5 groups: (1) normal control group; (2) ischemia group; (3) I/R group; (4) ischemia group with HB-EGF (400 μg/kg), and (5) I/R group with HG-EGF (400 μg/kg). c-Fos and c-Jun messenger RNAs and protein levels were determined by real-time quantitative polymerase chain reaction (PCR) and Western analyses, respectively. Statistical analysis was performed using ANOVA with Dunn's test. The messenger RNA levels of the c-Fos and c-Jun increased after intestinal ischemia or the intestinal reperfusion phase. HB-EGF pretreatment significantly decreased c-Fos and c-Jun messenger RNAs. The expression of protein levels of c-Fos and c-Jun were correlation with the expression of messenger RNA level. HB-EGF intestinal cytoprotection is mediated, in part, by downregulation of the expression of AP-1 transcription factor after intestinal I/R injury.

AB - The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury have been considered to be major contributing factors. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R injury. Recent studies have revealed that activator protein 1 (AP-1) family proteins including c-Fos and c-Jun potentially induce either the proliferation or apoptosis of the cells in the brain, heart, kidney, and liver. c-Fos and c-Jun expression has also been reported to be upregulated in postischemic intestinal epithelial cells (IECs). Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a potent cytoprotective factor in various pathologic conditions and plays a pivotal role in mediating the earliest cellular responses to injury. This study aims to examine whether HB-EGF, a proven intestinal cytoprotective molecule, exerts its protective effects through modulation of AP-1 transcription factor after intestinal I/R injury. Thirty rats were randomly divided into the following 5 groups: (1) normal control group; (2) ischemia group; (3) I/R group; (4) ischemia group with HB-EGF (400 μg/kg), and (5) I/R group with HG-EGF (400 μg/kg). c-Fos and c-Jun messenger RNAs and protein levels were determined by real-time quantitative polymerase chain reaction (PCR) and Western analyses, respectively. Statistical analysis was performed using ANOVA with Dunn's test. The messenger RNA levels of the c-Fos and c-Jun increased after intestinal ischemia or the intestinal reperfusion phase. HB-EGF pretreatment significantly decreased c-Fos and c-Jun messenger RNAs. The expression of protein levels of c-Fos and c-Jun were correlation with the expression of messenger RNA level. HB-EGF intestinal cytoprotection is mediated, in part, by downregulation of the expression of AP-1 transcription factor after intestinal I/R injury.

KW - Activator protein-1 transcription factor

KW - c-Fos

KW - c-Jun

KW - Heparin-binding epidermal growth factor-like growth factor

KW - Ischemia-reperfusion injury

KW - Small intestine

UR - http://www.scopus.com/inward/record.url?scp=78049467094&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78049467094&partnerID=8YFLogxK

U2 - 10.1159/000318142

DO - 10.1159/000318142

M3 - Article

VL - 99

SP - 241

EP - 246

JO - Neonatology

JF - Neonatology

SN - 1661-7800

IS - 4

ER -