title: Transforming growth factor-beta 3 alters intestinal smooth muscle function: implications for gastroschisis-related intestinal dysfunction.
abstract: BACKGROUND
  Gastroschisis (GS) is a congenital abdominal wall defect that results in the development of GS-related intestinal dysfunction (GRID). Transforming growth factor-β, 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-β3 on intestinal smooth muscle function and contractile gene expression.
  
  
  METHODS
  Archived human intestinal tissue was analyzed using immunohistochemistry and RT-PCR for TGF-β isoforms and markers of smooth muscle gene and micro-RNA contractile phenotype. Intestinal motility was measured in neonatal rats ± TGF-β3 (0.2 and 1 mg/kg). Human intestinal smooth muscle cells (hiSMCs) were incubated with fetal bovine serum ± 100 ng/ml of TGF-β 3 isoforms for 6, 24 and 72 h. The effects of TGF-β3 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-β3 and elevated levels of micro-RNA 143 & 145 in the intestinal smooth muscle. Rats had significantly decreased intestinal transit when exposed to TGF-β3 in a dose-dependent manner compared with Sham animals. TGF-β3 significantly increased hiSMC gel contraction and contractile protein gene and micro-RNA expression.
  
  
  CONCLUSIONS
  TGF-β3 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.
authors.affiliation: Department of Pediatric Surgery, The University of Texas Medical School at Houston, 6431 Fannin Street, MSB 5.222, Houston, TX, 77030, USA, Stacey.D.Moore-Olufemi@uth.tmc.edu.
authors.forename: S D
authors.initials: SD
authors.lastname: Moore-Olufemi
authors.forename: A B
authors.initials: AB
authors.lastname: Olsen
authors.forename: D M
authors.initials: DM
authors.lastname: Hook-Dufresne
authors.forename: V
authors.initials: V
authors.lastname: Bandla
authors.forename: C S
authors.initials: CS
authors.lastname: Cox
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects; D020139:Gastroschisis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3