Transforming growth factor-beta 3 alters intestinal smooth muscle function: implications for gastroschisis-related intestinal dysfunction.
Dig Dis Sci
; 60(5): 1206-14, 2015 May.
Article
in En
| MEDLINE
| ID: mdl-25431043
ABSTRACT
BACKGROUND:
Gastroschisis (GS) is a congenital abdominal wall defect that results in the development of GS-related intestinal dysfunction (GRID). Transforming growth factor-ß, 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-ß3 on intestinal smooth muscle function and contractile gene expression.METHODS:
Archived human intestinal tissue was analyzed using immunohistochemistry and RT-PCR for TGF-ß isoforms and markers of smooth muscle gene and micro-RNA contractile phenotype. Intestinal motility was measured in neonatal rats ± TGF-ß3 (0.2 and 1 mg/kg). Human intestinal smooth muscle cells (hiSMCs) were incubated with fetal bovine serum ± 100 ng/ml of TGF-ß 3 isoforms for 6, 24 and 72 h. The effects of TGF-ß3 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).RESULTS:
GS infants had increased immunostaining of TGF-ß3 and elevated levels of micro-RNA 143 & 145 in the intestinal smooth muscle. Rats had significantly decreased intestinal transit when exposed to TGF-ß3 in a dose-dependent manner compared with Sham animals. TGF-ß3 significantly increased hiSMC gel contraction and contractile protein gene and micro-RNA expression.CONCLUSION:
TGF-ß3 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.
Full text:
1
Database:
MEDLINE
Main subject:
Gastroschisis
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Myocytes, Smooth Muscle
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Transforming Growth Factor beta3
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Gastrointestinal Motility
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Intestinal Mucosa
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Muscle Contraction
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Muscle, Smooth
Limits:
Animals
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Humans
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Infant
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Male
Language:
En
Year:
2015
Type:
Article