Membrane Permeant Inhibitor of Myosin Light Chain Kinase Worsens Survival in Murine Polymicrobial Sepsis.

ABSTRACT:

Abstract

Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Genetic deletion of myosin light chain kinase (MLCK) reverses intestinal hyperpermeability and improves survival in a murine model of intra-abdominal sepsis. In an attempt to determine whether these findings could be translated using a more clinically relevant strategy, this study aimed to determine if pharmacologic inhibition of MLCK using the membrane permeant inhibitor of MLCK (PIK) improved gut barrier function and survival following sepsis. C57BL/6 mice underwent cecal ligation and puncture to induce sepsis and were then randomized to receive either PIK or vehicle. Unexpectedly, PIK significantl

SUBMITTER: Sun Y 

PROVIDER: S-EPMC8368082 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature