ERK and p38 MAP kinase pathways are mediators of intestinal epithelial wound-induced signal transduction.
Repair of gastrointestinal epithelial injury involves cell migration, proliferation, and specific gene expression. The pathways responsible for epithelial wound signal transduction are poorly understood. Mechanical wounding of IEC-6 cell monolayers resulted in rapid activation of the extracellular signal-regulated kinase (ERK) and p38 MAP kinase pathways, while c-Jun amino-terminal protein kinases were not significantly activated. Two minutes after wounding cells at the wound edge strongly expressed cytoplasmic phospho-ERK. By five minutes, immunostaining was concentrated within the nucleus. Consistent with activated MAP kinase signaling cascades (which phosphorylate transcription factors implicated in immediate-early gene induction), monolayer wounding resulted in greater than 30- and 8-fold increases in c-Fos and early growth response-1 mRNA by Northern blot analysis, peaking at 20 minutes. Only slight increases in c-Jun mRNA were detected. Thus, intestinal epithelial wound signal transduction is, at least in part, mediated by activation of ERK and p38 MAP kinase signaling cascades. ERK and p38 pathways may regulate pathophysiologically relevant genes in wound repair by the induction of transcription factors.
Dieckgraefe
B K
BK
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. dieck@im.wustl.edu
Weems
D M
DM
Santoro
S A
SA
Alpers
D H
DH
D000818:Animals; D015152:Blotting, Northern; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000293:injuries; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases