Evidence map›Paper›PMID 18586956›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2008

TIMAP is a positive regulator of pulmonary endothelial barrier function.

Csilla Csortos, Istvan Czikora, Natalia V Bogatcheva, Djanybek M Adyshev, Christophe Poirier, Gabor Olah, Alexander D Verin

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.3field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 41 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Csilla CsortosDepartment of Medical Chemistry, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
Istvan Czikora
Natalia V Bogatcheva
Djanybek M Adyshev
Christophe Poirier
Gabor Olah
Alexander D Verin
Augusta University · USUniversity of Chicago · USUniversity of Debrecen · HU

Funding

Tissue Culture Biomechanical CoreP01HL058064 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LAL, RATNESHWAR · 1998 to 2012
$27.8M
Microtubules in lung endothelial cell barrier regulationR01HL067307 · NHLBI · UNIVERSITY OF CHICAGO · PI VERIN, ALEXANDER D · 2001 to 2009
$2.5M
ATP in Lung Endothelial Barrier EnhancementR01HL083327 · NHLBI · UNIVERSITY OF CHICAGO · PI VERIN, ALEXANDER D · 2006 to 2009
$1.5M
ALK/SMAD Signaling in TGF beta-induced EC PermeabilityR01HL080675 · NHLBI · UNIVERSITY OF CHICAGO · PI VERIN, ALEXANDER D · 2005 to 2008
$1.5M
NHLBI NIH HHS HL-083327NHLBI NIH HHS HL-58064NHLBI NIH HHS HL-67307NHLBI NIH HHS HL-80675
6 · The paper itself

Abstract

TGF-beta-inhibited membrane-associated protein, TIMAP, is expressed at high levels in endothelial cells (EC). It is regarded as a member of the MYPT (myosin phosphatase target subunit) family of protein phosphatase 1 (PP1) regulatory subunits; however, its function in EC is not clear. In our pull-down experiments, recombinant TIMAP binds preferentially the beta-isoform of the catalytic subunit of PP1 (PP1cbeta) from pulmonary artery EC. As PP1cbeta, but not PP1calpha, binds with MYPT1 into functional complex, these results suggest that TIMAP is a novel regulatory subunit of myosin phosphatase in EC. TIMAP depletion by small interfering RNA (siRNA) technique attenuates increases in transendothelial electrical resistance induced by EC barrier-protective agents (sphingosine-1-phosphate, ATP) and enhances the effect of barrier-compromising agents (thrombin, nocodazole) demonstrating a barrier-protective role of TIMAP in EC. Immunofluorescent staining revealed colocalization of TIMAP with membrane/cytoskeletal protein, moesin. Moreover, TIMAP coimmunoprecipitates with moesin suggesting the involvement of TIMAP/moesin interaction in TIMAP-mediated EC barrier enhancement. Activation of cAMP/PKA cascade by forskolin, which has a barrier-protective effect against thrombin-induced EC permeability, attenuates thrombin-induced phosphorylation of moesin at the cell periphery of control siRNA-treated EC. On the contrary, in TIMAP-depleted EC, forskolin failed to affect the level of moesin phosphorylation at the cell edges. These results suggest the involvement of TIMAP in PKA-mediated moesin dephosphorylation and the importance of this dephosphorylation in TIMAP-mediated EC barrier protection.

Indexed as

Amino Acid SequenceBase SequenceBinding SitesCells, CulturedColforsinCyclic AMP-Dependent Protein KinasesDNA PrimersElectric ImpedanceEndothelial CellsHumansIsoenzymesMembrane ProteinsMicrofilament ProteinsProtein Phosphatase 1Pulmonary ArteryRecombinant Fusion ProteinsColforsinCyclic AMP-Dependent Protein KinasesDNA PrimersIsoenzymesMembrane ProteinsMicrofilament ProteinsmoesinPPP1CC protein, humanPPP1R16B protein, humanProtein Phosphatase 1Recombinant Fusion ProteinsRNA, Small InterferingThrombin

Identifiers

PMID18586956
PMCPMC2536797
OpenAlexW2106593693

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.