Evidence map›Paper›PMID 22049076›Full record

ArticleThe Journal of biological chemistry2011

Myocardin-related transcription factor-A complexes activate type I collagen expression in lung fibroblasts.

Larry L Luchsinger, Cassandra A Patenaude, Barbara D Smith, Matthew D Layne

Open access · hybridAbstract read
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. Cited by 74 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 3% 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

74 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.

  1. Pooled it
  2. Actin cytoskeletal dynamics in hepatic myofibroblasts and fibrosis.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. The Role of Myofibroblasts in Physiological and Pathological Tissue Repair.Cold Spring Harbor perspectives in biology · 2023
    Review
  14. Review
  15. Article
  16. Update on Novel Targeted Therapy for Pleural Organization and Fibrosis.International journal of molecular sciences · 2022
    Review
  17. Review
  18. Review
  19. Article
  20. Expression of serum response factor in the lung mesenchyme is essential for development of pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2021
    Article

14 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Larry L LuchsingerDepartment of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118.
Cassandra A PatenaudeDepartment of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118.
Barbara D SmithDepartment of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118. Electronic address: bdsmith@bu.edu.
Matthew D LayneDepartment of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118. Electronic address: mlayne@bu.edu.
Boston University · US

Funding

Collagen Transcription and Lung FibrosisR01HL068094 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SMITH, BARBARA DAVIS · 2001 to 2009
$3.3M
Training Program in Cardiovascular Biology: Pre-DoctoralT32HL007969 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAVID, KATYA · 2003 to 2019
$3.2M
Role of ACLP in Vascular Smooth Muscle BiologyR01HL078869 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LAYNE, MATTHEW D · 2007 to 2011
$2.2M
NHLBI NIH HHS HL078869NHLBI NIH HHS HL68094NHLBI NIH HHS R01 HL068094NHLBI NIH HHS R01 HL078869NHLBI NIH HHS T32 HL007969
6 · The paper itself

Abstract

Pulmonary fibrosis is characterized by the excessive deposition of a collagen-rich extracellular matrix. The accumulation of collagen within the lung interstitium leads to impaired respiratory function. Furthermore, smooth muscle actin-positive myofibroblasts within the fibrotic lung contribute to disease progression. Because collagen and smooth muscle cell α-actin are coordinately expressed in the setting of fibrosis, the hypothesis was tested that specific transcriptional regulators of the myocardin family might also regulate collagen gene expression in myofibroblasts. Myocardin-related transcription factors (MRTFs), through their interaction with the serum-response factor (SRF) on CArG box regulatory elements (CC(A/T)6GG), are important regulators of myofibroblast differentiation. MRTF-A transactivated type I collagen gene reporters as much as 100-fold in lung myofibroblasts. Loss of functional MRTF-A using either a dominant negative MRTF-A isoform, shRNA targeting MRTF-A, or genetic deletion of MRTF-A in lung fibroblasts significantly disrupted type I collagen synthesis relative to controls. Analysis of the COL1A2 proximal promoter revealed a noncanonical CArG box (CCAAACTTGG), flanked by several Sp1 sites important for MRTF-A activation. Chromatin immunoprecipitation experiments confirmed the co-localization of MRTF-A, SRF, and Sp1 bound to the same region of the COL1A2 promoter. Mutagenesis of either the noncanonical CArG box or the Sp1 sites significantly disrupted MRTF-A activation of COL1A2. Together, our findings show that MRTF-A is an important regulator of collagen synthesis in lung fibroblasts and exhibits a dependence on both SRF and Sp1 function to enhance collagen expression.

Indexed as

Gene Expression RegulationAnimalsCell DifferentiationCell LineCollagen Type IDNA-Binding ProteinsFibroblastsHumansLungMiceOncogene Proteins, FusionRatsSerum Response FactorSp1 Transcription FactorTrans-ActivatorsTranscription FactorsCollagen Type IDNA-Binding ProteinsMRTFA protein, humanMrtfa protein, mousemyocardin-related transcription factor-A, ratOncogene Proteins, FusionSerum Response FactorSp1 Transcription FactorTrans-ActivatorsTranscription Factors

Identifiers

PMID22049076
PMCPMC3243519
OpenAlexW2049777179

What Socratic 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 Socratic graph.