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Transforming growth factor-beta 3 alters intestinal smooth muscle function: implications for gastroschisis-related intestinal dysfunction.


ABSTRACT: Gastroschisis (GS) is a congenital abdominal wall defect that results in the development of GS-related intestinal dysfunction (GRID). Transforming growth factor-?, a pro-inflammatory cytokine, has been shown to cause organ dysfunction through alterations in vascular and airway smooth muscle. The purpose of this study was to evaluate the effects of TGF-?3 on intestinal smooth muscle function and contractile gene expression.Archived human intestinal tissue was analyzed using immunohistochemistry and RT-PCR for TGF-? isoforms and markers of smooth muscle gene and micro-RNA contractile phenotype. Intestinal motility was measured in neonatal rats ± TGF-?3 (0.2 and 1 mg/kg). Human intestinal smooth muscle cells (hiSMCs) were incubated with fetal bovine serum ± 100 ng/ml of TGF-? 3 isoforms for 6, 24 and 72 h. The effects of TGF-?3 on motility, hiSMC contractility and hiSMC contractile phenotype gene and micro-RNA expression were measured using transit, collagen gel contraction assay and RT-PCR analysis. Data are expressed as mean ± SEM, ANOVA (n = 6-7/group).GS infants had increased immunostaining of TGF-?3 and elevated levels of micro-RNA 143 & 145 in the intestinal smooth muscle. Rats had significantly decreased intestinal transit when exposed to TGF-?3 in a dose-dependent manner compared with Sham animals. TGF-?3 significantly increased hiSMC gel contraction and contractile protein gene and micro-RNA expression.TGF-?3 contributed to intestinal dysfunction at the organ level, increased contraction at the cellular level and elevated contractile gene expression at the molecular level. A hyper-contractile response may play a role in the persistent intestinal dysfunction seen in GRID.

SUBMITTER: Moore-Olufemi SD 

PROVIDER: S-EPMC4427617 | BioStudies | 2015-01-01T00:00:00Z

SECONDARY ACCESSION(S): NM_001299

REPOSITORIES: biostudies

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