Developmental regulation of transforming growth factor beta-mediated collagen synthesis in human intestinal muscle cells.
OBJECTIVE
The intestinal wall is formed by smooth muscle and the regulated deposition of specific collagen types. This study is the first to examine transforming growth factor beta (TGF-beta) in human fetal intestinal muscle. Studies localized TGF-beta within the muscularis propria, identified the cellular source, measured TGF-beta, and determined effects on collagen synthesis from 10 to 21 weeks of gestation.


METHODS
Localization of TGF-beta within the intestinal wall and in cultured cells was determined immunohistochemically. TGF-beta was measured by the CCL-64 cell growth inhibition assay. Collagen production was assayed as the uptake of 3H-proline into collagenase-digestible protein. Collagen types were identified by polyacrylamide slab gel electrophoresis and quantitated by densitometry. Experiments were performed in TGF-beta (50-200 pg/mL) or anti-TGF-beta (50-200 micrograms/mL).


RESULTS
TGF-beta 1 was localized in muscle cells of the muscularis propria and in culture. Muscle cells produced 340% more TGF-beta at 11 weeks of gestation than at 20 weeks. At 10 weeks of gestation, TGF-beta inhibited collagen production by 38%, but stimulated collagen synthesis by 70% at 21 weeks of gestation. TGF-beta altered the expression of individual collagen chains in an age-specific manner.


CONCLUSIONS
Smooth muscle cells secrete TGF-beta during human fetal intestinal development. TGF-beta stimulates or inhibits the expression of specific collagen chains depending on gestational age.
Department of Pediatrics, University of California, San Francisco, USA.
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Johnson
D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000196:embryology*; D009130:Muscle, Smooth / Q000166:cytology / Q000196:embryology*; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D016212:Transforming Growth Factor beta; D003094:Collagen