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Updated: Feb 6, 2026

Recapitulating Suckling-to-Weaning Transition In Vitro using Fetal Intestinal Organoids
Published on: November 15, 2019
Mechanical stretch modulates TGF-beta1 and alpha1(I) collagen expression in fetal human intestinal smooth muscle
1Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143, USA.
Abstract:
Intestinal muscle undergoes stretch intermittently during peristalsis and persistently proximal to obstruction. The influence of this pervasive biomechanical force on developing smooth muscle cell function remains unknown. We adapted a novel in vitro system to study whether stretch modulates transforming growth factor-beta1 (TGF-beta1) and type I collagen protein and component alpha1 chain [alpha1(I) collagen] expression in fetal human intestinal smooth muscle cells. Primary confluent cells at 20-wk gestation, cultured on flexible silicone membranes, were subjected to two brief stretches or to 18 h tonic stretch. Nonstretched cultures served as controls. TGF-beta1 protein was measured by ELISA and type I collagen protein was assayed by Western blot. TGF-beta1 and alpha1(I) collagen mRNA abundance was determined by Northern blot analysis, quantitated by phosphorimaging, and normalized to 18S rRNA. Transcription was examined by nuclear run-on assay. Tonic stretch increased TGF-beta1 protein 40%, type I collagen protein 100%, TGF-beta1 mRNA content 2.16-fold, and alpha1(I) collagen mRNA 3.80-fold and enhanced transcription of TGF-beta1 and alpha1(I) collagen by 3.1- and 4.25-fold, respectively. Brief stretch stimulated a 50% increase in TGF-beta1 mRNA content but no change in alpha1(I) collagen. Neutralizing anti-TGF-beta1 ablated stretch-mediated effects on alpha1(I) collagen. Therefore, stretch upregulates transcription for TGF-beta1, which stimulates alpha1(I) collagen gene expression in smooth muscle from developing gut.
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