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

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12 Citations (Scopus)


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
Issue number4
Publication statusPublished - Jun 2011
Externally publishedYes



  • 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

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