title: Deletion of myosin light chain kinase in endothelial cells has a minor effect on the lipopolysaccharide-induced increase in microvascular endothelium permeability in mice.
abstract: There is a current view that myosin light chain kinase (MLCK) plays a critical role in endothelial permeability. To investigate the functions of MLCK in endothelial cells in vivo, we generated a mouse model in which MLCK was selectively deleted by crossing Mylk1 floxed mice with Tie2/cre transgenic mice. Knocking out Mylk1 from endothelial cells had no effect on the global phenotype of the mice, including body weight and blood pressure. Lipopolysaccharide (LPS)-mediated septic death was also not altered in the knockout (KO) mice. Consistently, LPS-induced inflammatory injury and the increase in microvascular permeability in the main organs, including the lung and the kidney, was not significantly attenuated in KO mice as compared with wild-type mice. However, the LPS-induced microvascular hyperpermeability of the esophagus and the eyeballs was attenuated in KO mice. We also found that the LPS-mediated increase in the number of caveolae in the endothelial cells of the esophagus was significantly reduced in KO mice. Our results do not support a role for endothelial cell MLCK in the pathogenesis of inflammatory diseases.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Ning
authors.initials: N
authors.lastname: Lv
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lu
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zheng
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Peng
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: He
authors.forename: Fan-Qing
authors.initials: FQ
authors.lastname: Meng
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Zhu
authors.forename: Hua-Qun
authors.initials: HQ
authors.lastname: Chen
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004947:Esophagus / Q000166:cytology / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000201:enzymology* / Q000209:etiology / Q000401:mortality; D019426:Integrases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009219:Myosin-Light-Chain Kinase / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D042787:Receptor, TIE-2; D015996:Survival Rate
chemical_list: D008070:Lipopolysaccharides; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse; D009219:Myosin-Light-Chain Kinase; C045073:Cre recombinase; D019426:Integrases