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

Abstract

Background and Aims: The intestinal wait is formed by smooth muscle and the regulated deposition of specific collagen types. This study is the first to examine transforming growth factor β (TGF-β) in human fetal intestinal muscle. Studies localized TGF-β within the muscularis propria, identified the cellular source, measured TGF-β, and determined effects on collagen synthesis from 10 to 21 weeks of gestation. Methods: Localization of TGF-β within the intestinal wall and in cultured cells was determined immunohistochemically. TGF-β 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-β (50-200 pg/mL) or anti-TGF-β (50-200 μg/mL). Results: TGF-β1 was localized in muscle cells of the muscularis propria and in culture. Muscle cells produced 340% more TGF-β at 11 weeks of gestation than at 20 weeks. At 10 weeks of gestation, TGF-β inhibited collagen production by 38%, but stimulated collagen synthesis by 70% at 21 weeks of gestation. TGF-β altered the expression of individual collagen chains in an age-specific manner. Conclusions: Smooth muscle cells secrete TGF-β during human fetal intestinal development. TGF-β stimulates or inhibits the expression of specific collagen chains depending on gestational age.