Heparin-binding epidermal growth factor-like growth factor downregulates expression of activator protein-1 transcription factor after intestinal ischemia-reperfusion injury.
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.
Department of Pediatric Surgery, Department of Pediatrics, Chang Gung Children's Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Chih-Cheng
CC
Luo
Yung-Ching
YC
Ming
Hsun-Chin
HC
Chao
Shih-Ming
SM
Chu
See-Tong
ST
Pang
D000818:Animals; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D018808:Transcription Factor AP-1