TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS

Christophe Poirier, Boris A. Gorshkov, Marina A. Zemskova, Natalia V. Bogatcheva, Alexander D. Verin

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

TIMAP is a regulatory subunit of protein phosphatase 1, whose role remains largely unknown. Our recent data suggested that TIMAP is involved in the regulation of barrier function in cultured pulmonary endothelial monolayers [Csortos et al., 2008. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L440-L450]. Here we showed that TIMAP depletion exacerbates lipopolysaccharide (LPS)-induced vascular leakage in murine lung, suggesting that TIMAP has a barrier-protective role in vivo. Real-Time RT PCR analysis revealed that treatment with LPS significantly suppressed Timap mRNA level. This suppression was not achieved via the down-regulation of Timap promoter activity, suggesting that LPS decreased Timap mRNA stability. Pretreatment with protein kinase A (PKA) inhibitor H-89 reduced TIMAP mRNA level, whereas pretreatment with PKA activator, bnz-cAMP, increased this level and attenuated LPS-induced decrease in TIMAP mRNA. Altogether, these data confirmed the barrier-protective role of TIMAP and suggested that barrier-disruptive and barrier-protective agents may employ modulation of TIMAP expression as a mechanism affecting barrier permeability.

Original languageEnglish (US)
Pages (from-to)334-337
Number of pages4
JournalRespiratory Physiology and Neurobiology
Volume179
Issue number2-3
DOIs
StatePublished - Dec 15 2011
Externally publishedYes

Keywords

  • Barrier dysfunction
  • LPS
  • PKA
  • PPP1R16B
  • TIMAP

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

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