Heparin-binding EGF-like growth factor is an autocrine growth factor for rat gastric epithelial cells.
We examined the biological action and expression of heparin-binding EGF-like growth factor (HB-EGF) in a rat gastric mucosal cell line, RGM1. HB-EGF stimulated DNA synthesis of RGM1 cells in a dose-dependent manner. Mitogenic effect of HB-EGF was as potent as that of other known mitogens for gastric epithelial cells, such as hepatocyte growth factor (HGF) and transforming growth factor (TGF)-alpha. Northern blot analysis showed that RGM1 cells as well as rat gastric mucosal tissue expressed a 2.5-kilobase transcript of HB-EGF. Not only HB-EGF and TGF-alpha but also HGF caused a rapid induction of HB-EGF mRNA in the cells. Treatment with heparitinase which destroys heparan sulfate proteoglycan (HSPG) or with chlorate which inhibits sulfation of HSPG diminished [3H]thymidine incorporation of RGM1 cells in serum-free medium. In addition, a synthetic peptide corresponding to the heparin-binding domain of HB-EGF inhibits the DNA synthesis of RGM1 cells in serum-free medium in a dose-dependent manner. These results suggest that HB-EGF is an autocrine and paracrine growth factor for gastric epithelial cells and may play significant roles in mucosal repair of the stomach in cooperation with other growth factors.
Miyazaki
Y
Y
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Shinomura
Y
Y
Higashiyama
S
S
Kanayama
S
S
Higashimoto
Y
Y
Tsutsui
S
S
Zushi
S
S
Taniguchi
N
N
Matsuzawa
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D016895:Culture Media, Serum-Free; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D006493:Heparin; D004247:DNA; D013936:Thymidine