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Myosin light chain kinase mediates intestinal barrier disruption following burn injury.
PLoS One. 2012; 7(4):e34946.Plos

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.

METHODOLOGY/PRINCIPAL FINDINGS

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/SIGNIFICANCE

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.

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Authors+Show Affiliations

Chen C
State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Burn Research, Third Military Medical University, Southwest Hospital, Chongqing, China.
Wang P
No affiliation info available
Su Q
No affiliation info available
Wang S
No affiliation info available
Wang F
No affiliation info available

MeSH

AnimalsAzepinesBurnsDisease Models, AnimalEnzyme InhibitorsIntestinal MucosaMaleMiceMice, Inbred BALB CMyosin Light ChainsMyosin-Light-Chain KinasePermeabilityPhosphorylationTight JunctionsZonula Occludens-1 Protein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22529961

Citation

Chen, Chuanli, et al. "Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption Following Burn Injury." PloS One, vol. 7, no. 4, 2012, pp. e34946.
Chen C, Wang P, Su Q, et al. Myosin light chain kinase mediates intestinal barrier disruption following burn injury. PLoS One. 2012;7(4):e34946.
Chen, C., Wang, P., Su, Q., Wang, S., & Wang, F. (2012). Myosin light chain kinase mediates intestinal barrier disruption following burn injury. PloS One, 7(4), e34946. https://doi.org/10.1371/journal.pone.0034946
Chen C, et al. Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption Following Burn Injury. PLoS One. 2012;7(4):e34946. PubMed PMID: 22529961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Myosin light chain kinase mediates intestinal barrier disruption following burn injury. AU - Chen,Chuanli, AU - Wang,Pei, AU - Su,Qin, AU - Wang,Shiliang, AU - Wang,Fengjun, Y1 - 2012/04/18/ PY - 2011/12/12/received PY - 2012/03/07/accepted PY - 2012/4/25/entrez PY - 2012/4/25/pubmed PY - 2012/12/10/medline SP - e34946 EP - e34946 JF - PloS one JO - PLoS One VL - 7 IS - 4 N2 - 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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22529961/Myosin_light_chain_kinase_mediates_intestinal_barrier_disruption_following_burn_injury_ L2 - https://dx.plos.org/10.1371/journal.pone.0034946 DB - PRIME DP - Unbound Medicine ER -