Evidence map›Paper›PMID 20709086›Full record

ArticleMicrovascular research2010

Calpain- and talin-dependent control of microvascular pericyte contractility and cellular stiffness.

Maciej Kotecki, Adam S Zeiger, Krystyn J Van Vliet, Ira M Herman

Open access · greenAbstract read
In one paragraph

Article in Microvascular research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Talin determines the nanoscale architecture of focal adhesions.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Regulation of blood flow in the retinal trilaminar vascular network.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014
    Article
  17. Pericyte-endothelial crosstalk: implications and opportunities for advanced cellular therapies.Translational research : the journal of laboratory and clinical medicine · 2014
    Review
  18. Article
  19. Article
  20. Article
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

4 authors at 2 institutions in 1 country.

Maciej KoteckiDepartment of Physiology, and The Center for Innovations in Wound Healing Research, Tufts University School of Medicine, Boston, MA 02111, USA.
Adam S Zeiger
Krystyn J Van Vliet
Ira M Herman
Massachusetts Institute of Technology · USTufts University · US

Funding

Regulating retinal microvascular morphogenesisR01EY015125 · NEI · TUFTS UNIVERSITY BOSTON · PI HERMAN, IRA M · 2004 to 2010
$1.7M
A new approach to the treatment of Retinopathy of PrematurityK08EY019533 · NEI · UNIVERSITY OF VIRGINIA · PI YATES, PAUL A. · 2009 to 2013
$959k
Pericytes, pathological angiogenesis and diabetic retinopathyR21EY019553 · NEI · TUFTS UNIVERSITY BOSTON · PI HERMAN, IRA M · 2009 to 2010
$452k
NEI NIH HHS EY 15125NEI NIH HHS EY 19533NEI NIH HHS K08 EY019533NEI NIH HHS R01 EY015125NEI NIH HHS R21 EY019553
6 · The paper itself

Abstract

Pericytes surround capillary endothelial cells and exert contractile forces modulating microvascular tone and endothelial growth. We previously described pericyte contractile phenotype to be Rho GTPase- and α-smooth muscle actin (αSMA)-dependent. However, mechanisms mediating adhesion-dependent shape changes and contractile force transduction remain largely equivocal. We now report that the neutral cysteine protease, calpain, modulates pericyte contractility and cellular stiffness via talin, an integrin-binding and F-actin associating protein. Digital imaging and quantitative analyses of living cells reveal significant perturbations in contractile force transduction detected via deformation of silicone substrata, as well as perturbations of mechanical stiffness in cellular contractile subdomains quantified via atomic force microscope (AFM)-enabled nanoindentation. Pericytes overexpressing GFP-tagged talin show significantly enhanced contractility (~two-fold), which is mitigated when either the calpain-cleavage resistant mutant talin L432G or vinculin are expressed. Moreover, the cell-penetrating, calpain-specific inhibitor termed CALPASTAT reverses talin-enhanced, but not Rho GTP-dependent, contractility. Interestingly, our analysis revealed that CALPASTAT, but not its inactive mutant, alters contractile cell-driven substrata deformations while increasing mechanical stiffness of subcellular contractile regions of these pericytes. Altogether, our results reveal that calpain-dependent cleavage of talin modulates cell contractile dynamics, which in pericytes may prove instrumental in controlling normal capillary function or microvascular pathophysiology.

Indexed as

Cell ShapeMechanotransduction, CellularAnimalsCalpainCattleCells, CulturedCysteine Proteinase InhibitorsDose-Response Relationship, DrugElasticityMiceMicroscopy, Atomic ForceMicrovesselsMutationPericytesPhenotypeRecombinant Fusion ProteinsCalpaincalpastatCysteine Proteinase InhibitorsRecombinant Fusion ProteinsrhoA GTP-Binding ProteinTalinTln1 protein, mouseVinculin

Identifiers

PMID20709086
PMCPMC2981705
OpenAlexW2103161436

What OpenQuestion holds

Textmetadata
LicenceTDM
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.