The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Activated Protein C Mediates Novel Lung Endothelial Barrier Enhancement
Open accessAbstract
Increased endothelial cell (EC) permeability is central to the pathophysiology of inflammatory syndromes such as sepsis and acute lung injury (ALI). Activated protein C (APC), a serine protease critically involved in the regulation of coagulation and inflammatory processes, improves sepsis survival through an unknown mechanism. We hypothesized a direct effect of APC to both prevent increased EC permeability and to restore vascular integrity after edemagenic agonists. We measured changes in transendothelial electrical resistance (TER) and observed that APC produced concentration-dependent attenuation of TER reductions evoked by thrombin. We next explored known EC barrier-protective signaling pathways and observed dose-dependent APC-mediated increases in cortical myosin light chain (MLC) phosphorylation in concert with cortically distributed actin polymerization, findings highly suggestive of Rac GTPase involvement. We next determined that APC directly increases Rac1 activity, with inhibition of Rac1 activity significantly attenuating APC-mediated barrier protection to thrombin challenge. Finally, as these signaling events were similar to those evoked by the potent EC barrier-enhancing agonist, sphingosine 1-phosphate (S1P), we explored potential cross-talk between endothelial protein C receptor (EPCR) and S1P1, the receptors for APC and S1P, respectively. EPCR-blocking antibody (RCR-252) significantly attenuated both APC-mediated barrier protection and increased MLC phosphorylation. We next observed rapid, EPCR and PI 3-kinase-dependent, APC-mediated phosphorylation of S1P1 on threonine residues consistent with S1P1 receptor activation. Co-immunoprecipitation studies demonstrate an interaction between EPCR and S1P1 upon APC treatment. Targeted silencing of S1P1 expression using siRNA significantly reduced APC-mediated barrier protection against thrombin. These data suggest that novel EPCR ligation and S1P1 transactivation results in EC cytoskeletal rearrangement and barrier protection, components potentially critical to the improved survival of APC-treated patients with severe sepsis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Angus, D. C., Linde-Zwirble, W. T., Lidicker, J., Clermont, G., Carcillo, J., & Pinsky, M. R. (2001) · Critical Care Medicine · doi:10.1097/00003246-200107000-00002 · Cited by 8,503
Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis
Bernard, G. R., Vincent, J.-L., Laterre, P.-F., LaRosa, S. P., Dhainaut, J.-F., Lopez-Rodriguez, A., Steingrub, J. S., Garber, G. E., Helterbrand, J. D., Ely, E. W., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103083441001 · Cited by 6,132
High-Dose Antithrombin III in Severe Sepsis: A Randomized Controlled Trial
Warren, B. L., Eid, A., Singer, P., Pillay, S. S., Carl, P., Novak, I., Chalupa, P., Atherstone, A., Pénzes, I., Kübler, A., et al. (2001) · JAMA · doi:10.1001/jama.286.15.1869 · Cited by 1,419
Deficiency of protein C in congenital thrombotic disease.
Griffin, J. H., Evatt, B., Zimmerman, T. S., Kleiss, A. J., & Wideman, C. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110385 · Cited by 1,250
Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics
Edwards, D. C., Sanders, L. C., Bokoch, G. M., & Gill, G. N. (1999) · Nature Cell Biology · doi:10.1038/12963 · Cited by 1,062
Cytoskeletal regulation of pulmonary vascular permeability
Dudek, S. M., & Garcia, J. G. N. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.4.1487 · Cited by 985
Self-citationAbraham, E., Reinhart, K., Opal, S., Demeyer, I., Doig, C., Rodriguez, A. L., Beale, R., Svoboda, P., Laterre, P. F., Simon, S., et al. (2003) · JAMA · doi:10.1001/jama.290.2.238 · Cited by 959
Garcia, J. G. N., Liu, F., Verin, A. D., Birukova, A., Dechert, M. A., Gerthoffer, W. T., Bamberg, J. R., & English, D. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12450 · Cited by 886
Self-citationActivation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway
Riewald, M., Petrovan, R. J., Donner, A., Mueller, B. M., & Ruf, W. (2002) · Science · doi:10.1126/science.1071699 · Cited by 831
Cheng, T., Liu, D., Griffin, J. H., Fernández, J. A., Castellino, F., Rosen, E. D., Fukudome, K., & Zlokovic, B. V. (2003) · Nature Medicine · doi:10.1038/nm826 · Cited by 560
Cited by
Levi, M., & van der Poll, T. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181c98d21 · Cited by 984
Inflammation, endothelium, and coagulation in sepsis
Schouten, M., Wiersinga, W. J., Levi, M., & van der Poll, T. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0607373 · Cited by 629
Heuberger, D. M., & Schuepbach, R. A. (2019) · Thrombosis Journal · doi:10.1186/s12959-019-0194-8 · Cited by 371
Structure, function and pathophysiology of protease activated receptors
Adams, M. N., Ramachandran, R., Yau, M.-K., Suen, J. Y., Fairlie, D. P., Hollenberg, M. D., & Hooper, J. D. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.01.003 · Cited by 370
Endotoxemia and sepsis mortality reduction by non-anticoagulant–activated protein C
Kerschen, E. J., Fernandez, J. A., Cooley, B. C., Yang, X. V., Sood, R., Mosnier, L. O., Castellino, F. J., Mackman, N., Griffin, J. H., & Weiler, H. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070404 · Cited by 305
Metadata
- Authors
- Finigan, J. H., Dudek, S. M., Singleton, P. A., Chiang, E. T., Jacobson, J. R., Camp, S. M., Ye, S. Q., & Garcia, J. G. N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 280
- Issue
- 17
- Pages
- 17286-17293
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2040968233
- Cited by
- 354
- References
- 48
- FWCI
- 18.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Activated Protein C Mediates Novel Lung Endothelial Barrier Enhancement. https://app.cochat.ai/papers/10.1074/jbc.m412427200
- The paper
- Finigan, J. H., Dudek, S. M., Singleton, P. A., Chiang, E. T., Jacobson, J. R., Camp, S. M., Ye, S. Q., & Garcia, J. G. N. (2005). Activated Protein C Mediates Novel Lung Endothelial Barrier Enhancement. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m412427200
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
