Regulation of amphiregulin and epiregulin expression in human colonic subepithelial myofibroblasts.
Amphiregulin and epiregulin belong to the epidermal growth factor (EGF) family, and act as mitogenic stimulators via binding to EGF receptors (EGFRs). Amphiregulin and epiregulin are thought to play a role in regenerative responses in the gastrointestinal tract. In this study, we investigated secretion of amphiregulin and epiregulin in human colonic subepithelial myofibroblasts (SEMFs). The mRNA expression and protein secretion of amphiregulin and epiregulin were evaluated by Northern blotting and Western blotting, respectively. The trophic effects of amphiregulin and epiregulin on SEMFs were analyzed by MTT assays. Amphiregulin and epiregulin mRNAs were not detected in unstimulated SEMFs. Among the various cytokines and growth factors, interleukin-1beta, tumor necrosis factor-alpha, and EGF strongly induced amphiregulin and epiregulin mRNA expression. These responses were markedly reduced by AG1478, a specific inhibitor of EGF receptor tyrosine kinases. Amphiregulin and epiregulin secretion were also detected at the protein level. MTT assays demonstrated that amphiregulin and epiregulin stimulate the proliferation of SEMFs. We demonstrated expression of amphiregulin and epiregulin in SEMFs. Amphiregulin and epiregulin may play an important role in the mechanism underlying wound healing in damaged colonic mucosa.
Inatomi
Osamu
O
Department of Internal Medicine, Shiga University of Medical Science, Otsu 520-2192, Japan.
Andoh
Akira
A
Yagi
Yuhki
Y
Bamba
Shigeki
S
Tsujikawa
Tomoyuki
T
Fujiyama
Yoshihide
Y
D066258:Amphiregulin; D019898:Autocrine Communication; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066260:Epiregulin; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D032390:Myoblasts, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C587848:AREG protein, human; D066258:Amphiregulin; D016207:Cytokines; D066255:EGF Family of Proteins; C587880:EREG protein, human; D066260:Epiregulin; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor