Developmentally regulated expression of matrix metalloproteinases during fetal rat colon morphogenesis.
To investigate the role of matrix metalloproteinases (MMPs) during gastrointestinal tract development, the expression of gelatinases (MMP-2 and MMP-9) was investigated during fetal rat colon morphogenesis. Fetal rat colons were separated into epithelial and mesenchymal fractions without cross contamination using a chelating agent and a dissecting microscope. Gelatinase activity measured using fluorescently labeled gelatin was higher in the mesenchymal than in the epithelial fraction; the developmental profile revealed that, in both fractions, gelatinase activity was enhanced during colon morphogenesis. During colonic gland formation, there was prominent MMP-2 activity, elevated MMP-2 mRNA expression, and an increase in the level of the active form of MMP-2 in the mesenchymal fraction. The mRNA expression of the tissue inhibitor of metalloproteinase 2 corresponded with an elevation in the level of the active form of MMP-2; the mRNA expression of the cell surface activator of MMP-2, membrane type matrix metalloproteinase 1, did not increase significantly. MMP-9 activity was low; only the pro-form was observed in the epithelial fraction at the end of fetal life. These results suggest that, during colon morphogenesis, MMP activity is under strict spatio-temporal control, and that the activity of MMP-2, which is regulated at both the transcriptional and proteolytic activation levels, is very much involved in rat colon morphogenesis.
Kurakata
Hidenori
H
Division of Gastroenterology and Hepatology, Department of Internal Medicine (Ohmori), School of Medicine, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan.
Oka
Masashi
M
Matsubara
Yasuo
Y
Niwa
Tohru
T
Utsunomiya
Hirotoshi
H
Fujishiro
Mitsuhiro
M
Miki
Kazumasa
K
Fukamachi
Hiroshi
H
Kubota
Syunichiro
S
Ichinose
Masao
M
D000818:Animals; D003106:Colon / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism*; D047109:Fetal Development / Q000235:genetics; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D009024:Morphogenesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9