Evidence map›Paper›PMID 15690088›Full record

ArticleThe Journal of clinical investigation2005

5' CArG degeneracy in smooth muscle alpha-actin is required for injury-induced gene suppression in vivo.

Jennifer A Hendrix, Brian R Wamhoff, Oliver G McDonald, Sanjay Sinha, Tadashi Yoshida, Gary K Owens

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

56 citing papers in PubMed, 101 citations in OpenAlex.

  1. Actin cytoskeletal dynamics in hepatic myofibroblasts and fibrosis.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  2. Article
  3. Article
  4. Methamphetamine induces thoracic aortic aneurysm/dissection through C/EBPβ.Biochimica et biophysica acta. Molecular basis of disease · 2022
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Upregulation of the actin cytoskeleton via myocardin leads to increased expression of type 1 collagen.Laboratory investigation; a journal of technical methods and pathology · 2017
    Article
  13. Article
  14. Article
  15. A New Editor of Smooth Muscle Phenotype.Circulation research · 2016
    Article
  16. Article
  17. Myocardin regulates vascular smooth muscle cell inflammatory activation and disease.Arteriosclerosis, thrombosis, and vascular biology · 2015
    Article
  18. Myocardin in biology and disease.Journal of biomedical research · 2015
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Jennifer A HendrixDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, USA.
Brian R Wamhoff
Oliver G McDonald
Sanjay Sinha
Tadashi Yoshida
Gary K Owens
University of Virginia · US

Funding

THE CONTRACTILE SYSTEM OF VASCULAR SMOOTH MUSCLEP01HL019242 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI OWENS, GARY K · 1985 to 2009
$16.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007267 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GARCIA-BLANCO, MARIANO A. · 1985 to 2024
$13.4M
MOLECULAR REGULATION OF SMOOTH MUSCLE DIFFERENTIATIONR01HL038854 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI OWENS, GARY K · 1987 to 2010
$3.7M
NHLBI NIH HHS P01 HL019242NHLBI NIH HHS P01 HL19242NHLBI NIH HHS R01 HL038854NHLBI NIH HHS R01 HL38854PHS HHS R3757353
6 · The paper itself

Abstract

CC(A/T)6GG-dependent (CArG-dependent) and serum response factor-dependent (SRF-dependent) mechanisms are required for gene expression in smooth muscle cells (SMCs). However, an unusual feature of many SMC-selective promoter CArG elements is that they contain a conserved single G or C substitution in their central A/T-rich region, which reduces binding affinity for ubiquitously expressed SRF. We hypothesized that this CArG degeneracy contributes to cell-specific expression of smooth muscle alpha-actin in vivo, since substitution of c-fos consensus CArGs for the degenerate CArGs resulted in relaxed specificity in cultured cells. Surprisingly, our present results show that these substitutions have no effect on smooth muscle-specific transgene expression during normal development and maturation in transgenic mice. However, these substitutions significantly attenuated injury-induced downregulation of the mutant transgene under conditions where SRF expression was increased but expression of myocardin, a smooth muscle-selective SRF coactivator, was decreased. Finally, chromatin immunoprecipitation analyses, together with cell culture studies, suggested that myocardin selectively enhanced SRF binding to degenerate versus consensus CArG elements. Our results indicate that reductions in myocardin expression and the degeneracy of CArG elements within smooth muscle promoters play a key role in phenotypic switching of smooth muscle cells in vivo, as well as in mediating responses of CArG-dependent smooth muscle genes and growth regulatory genes under conditions in which these 2 classes of genes are differentially expressed.

Indexed as

ActinsAnimalsChromatinChromatin ImmunoprecipitationEmbryo, MammalianGene Expression Regulation, DevelopmentalGrowthMiceMice, TransgenicMuscle, SmoothMyocardinMyocytes, Smooth MuscleNuclear ProteinsOrgan SpecificityPoint MutationProto-Oncogene Proteins c-fosActinsChromatinMyocardinNuclear ProteinsProto-Oncogene Proteins c-fosTrans-Activators

Identifiers

PMID15690088
PMCPMC546420
OpenAlexW2112886810

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.