Evidence map›Paper›PMID 21357420›Full record

ArticleThe Journal of biological chemistry2011

G protein-coupled receptor kinase-2 is a novel regulator of collagen synthesis in adult human cardiac fibroblasts.

Karen M D'Souza, Ricky Malhotra, Jennifer L Philip, Michelle L Staron, Tiju Theccanat, Valluvan Jeevanandam, Shahab A Akhter

RetractedOpen access · hybridAbstract readRetracted Publication
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Mechanotransduction in Wound Healing and Fibrosis.Journal of clinical medicine · 2020
    Review
  2. Article
  3. Cardiac Fibrosis: The Fibroblast Awakens.Circulation research · 2016
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. GRK2 in the heart: a GPCR kinase and beyond.Antioxidants & redox signaling · 2014
    Review
  10. Article
  11. Article
  12. Adenosine 2A receptor promotes collagen production by human fibroblasts via pathways involving cyclic AMP and AKT but independent of Smad2/3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. cAMP and Epac in the regulation of tissue fibrosis.British journal of pharmacology · 2012
    Review
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Karen M D'SouzaDepartment of Surgery, Section of Cardiac and Thoracic Surgery, University of Chicago Medical Center, Chicago, Illinois 60637, USA.
Ricky Malhotra
Jennifer L Philip
Michelle L Staron
Tiju Theccanat
Valluvan Jeevanandam
Shahab A Akhter
University of Chicago Medical Center · US

Funding

Myocardial Regulation of betaARK1 by Protein Kinase CK08HL081472 · NHLBI · UNIVERSITY OF CINCINNATI · PI AKHTER, SHAHAB A · 2005 to 2009
$667k
NHLBI NIH HHS HL081472NHLBI NIH HHS K08 HL081472
6 · The paper itself

Abstract

Cardiac fibroblasts (CF) make up 60-70% of the total cell number in the heart and play a critical role in regulating normal myocardial function and in adverse remodeling following myocardial infarction and the transition to heart failure. Recent studies have shown that increased intracellular cAMP can inhibit CF transformation and collagen synthesis in adult rat CF; however, mechanisms by which cAMP production is regulated in CF have not been elucidated. We investigated the potential role of G protein-coupled receptor kinase-2 (GRK2) in modulating collagen synthesis by adult human CF isolated from normal and failing left ventricles. Baseline collagen synthesis was elevated in failing CF and was not inhibited by β-agonist stimulation in contrast to normal controls. β-adrenergic receptor (β-AR) signaling was markedly uncoupled in the failing CF, and expression and activity of GRK2 were increased 3-fold. Overexpression of GRK2 in normal CF recapitulated a heart failure phenotype with minimal inhibition of collagen synthesis following β-agonist stimulation. In contrast, knockdown of GRK2 expression in normal CF enhanced cAMP production and led to greater β-agonist-mediated inhibition of basal and TGFβ-stimulated collagen synthesis versus control. Inhibition of GRK2 activity in failing CF by expression of the GRK2 inhibitor, GRK2ct, or siRNA-mediated knockdown restored β-agonist-stimulated inhibition of collagen synthesis and decreased collagen synthesis in response to TGFβ stimulation. GRK2 appears to play a significant role in regulating collagen synthesis in adult human CF, and increased activity of this kinase may be an important mechanism of maladaptive ventricular remodeling as mediated by cardiac fibroblasts.

Indexed as

AdultCollagenCyclic AMPFibroblastsG-Protein-Coupled Receptor Kinase 2Heart FailureHeart VentriclesHumansMyocardiumVentricular RemodelingCollagenCyclic AMPG-Protein-Coupled Receptor Kinase 2GRK2 protein, human

Identifiers

PMID21357420
PMCPMC3083230
OpenAlexW2008637244

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.