title: Myosin light chain kinase mediates intestinal barrier disruption following burn injury.
abstract: BACKGROUND
  Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction.
  
  
  RESULTS
  Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression.
  
  
  CONCLUSIONS
  The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury.
authors.affiliation: State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Burn Research, Third Military Medical University, Southwest Hospital, Chongqing, China.
authors.forename: Chuanli
authors.initials: C
authors.lastname: Chen
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Su
authors.forename: Shiliang
authors.initials: S
authors.lastname: Wang
authors.forename: Fengjun
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002056:Burns / Q000201:enzymology* / Q000473:pathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; D062826:Zonula Occludens-1 Protein; C056218:ML 9; D009219:Myosin-Light-Chain Kinase