Developmental regulation of transforming growth factor beta-mediated collagen synthesis in human intestinal muscle cells.

BACKGROUND & AIMS: 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.