title: Hydrostatic intestinal edema induced signaling pathways: potential role of mechanical forces.
abstract: BACKGROUND
  Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema.
  
  
  METHODS
  The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1-3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine.
  
  
  RESULTS
  Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength.
  
  
  CONCLUSIONS
  Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction.
authors.affiliation: Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Shinil K
authors.initials: SK
authors.lastname: Shah
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Fogle
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Aroom
authors.forename: Brijesh S
authors.initials: BS
authors.lastname: Gill
authors.forename: Stacey D
authors.initials: SD
authors.lastname: Moore-Olufemi
authors.forename: Fernando
authors.initials: F
authors.lastname: Jimenez
authors.forename: Karen S
authors.initials: KS
authors.lastname: Uray
authors.forename: Peter A
authors.initials: PA
authors.lastname: Walker
authors.forename: Randolph H
authors.initials: RH
authors.lastname: Stewart
authors.forename: Glen A
authors.initials: GA
authors.lastname: Laine
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cox
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002467:Cell Nucleus / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D017931:DNA Primers; D006487:Hemostasis; D006874:Hydrostatic Pressure; D007410:Intestinal Diseases / Q000503:physiopathology*; D007421:Intestine, Small / Q000033:anatomy & histology / Q000503:physiopathology*; D007819:Laryngeal Edema / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D018994:Myosin Light Chains / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: D017931:DNA Primers; D018994:Myosin Light Chains; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D052247:Nitric Oxide Synthase Type II