Expression and cytoprotective effect of protease-activated receptor-1 in gastric epithelial cells.
Thrombin is a serine protease involved in many physiological functions and its receptor. the protease-activated receptor-1 (PAR-1), has a wide tissue distribution. We hypothesized that PAR-1 is expressed in gastric epithelial cells and that thrombin can modulate defence mechanisms through PAR-1. The rat gastric epithelial cell line (RMG1) and gastric biopsy specimens from gastritis patients were used in the study. Reverse transcriptase polymerase chain reaction analysis showed that the thrombin receptors PAR-1, PAR3 and PAR-4 are expressed by RGM1 gastric epithelial cell line. Immunohistochemical and electron microspcopic studies also showed PAR-1 expression in human gastric epithelial cells. Thrombin stimulated the secretion of mucin and prostaglandin E2 (PGE2) formation in RGM1 cells in a dose-dependent manner. PAR-1 agonist also stimulated PGE2 formation. In addition, thrombin significantly increases the expression of the PGE2 receptors EP2-R and EP4-R in RGM1 cells. In conclusion, the results of the present study showed for the first time that gastric epithelial cells express thrombin receptors and that these receptors may play a protective role in the gastric mucosa.
Toyoda
N
N
Third Dept. of Internal Medicine, Mie University School of Medicine, Tsu City, Mie, Japan.
Gabazza
E C
EC
Inoue
H
H
Araki
K
K
Nakashima
S
S
Oka
S
S
Taguchi
Y
Y
Nakamura
M
M
Suzuki
Y
Y
Taguchi
O
O
Imoto
I
I
Suzuki
K
K
Adachi
Y
Y
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001711:Biotransformation / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005752:Gastric Mucins / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008855:Microscopy, Electron, Scanning; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D044463:Receptor, PAR-1; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis; D018179:Receptors, Thrombin / Q000096:biosynthesis* / Q000235:genetics*; D013917:Thrombin / Q000378:metabolism
D015415:Biomarkers; D005752:Gastric Mucins; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D018078:Receptors, Prostaglandin E; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; D013917:Thrombin; C112908:protease-activated receptor 4; D015232:Dinoprostone