Evidence map›Paper›PMID 34280336›Full record

ArticleAmerican journal of respiratory cell and molecular biology2021

HDAC6 Activates ERK in Airway and Pulmonary Vascular Remodeling of Chronic Obstructive Pulmonary Disease.

Yunchao Su, Weihong Han, Anita Kovacs-Kasa, Alexander D Verin, Laszlo Kovacs

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory cell and molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Ambient PMEnvironment & health (Washington, D.C.) · 2026
    Article
  3. The role and mechanism of histone deacetylase in COPD.Molecular and cellular biochemistry · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Serum Proteomic Profiling in Patients with Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Yunchao SuDepartment of Pharmacology and Toxicology.
Weihong HanDepartment of Pharmacology and Toxicology.
Anita Kovacs-KasaVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia; and.
Alexander D VerinVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia; and.
Laszlo KovacsDepartment of Pharmacology and Toxicology.
Augusta University · US

Funding

PFKFB3 in vascular remodelingR01HL134934 · NHLBI · AUGUSTA UNIVERSITY · PI HUO, YUQING, SU, YUNCHAO · 2017 to 2020
$2.3M
Airway and Lung Vascular Remodeling in COPDI01BX002035 · VA · CHARLIE NORWOOD VA MEDICAL CENTER · PI SU, YUNCHAO · 2015 to 2018
–
BLRD VA I01 BX002035NHLBI NIH HHS R01 HL134934
6 · The paper itself

Abstract

Chronic obstructive pulmonary disease (COPD) is a multisystemic respiratory disease that is associated with progressive airway and pulmonary vascular remodeling due to the increased proliferation of bronchial smooth muscles cells (BSMCs) and pulmonary arterial smooth muscle cells (PASMCs) and the overproduction of extracellular matrix (e.g., collagen). Cigarette smoke (CS) and several mediators, such as PDGF (platelet-derived growth factor) and IL-6, play critical roles in COPD pathogenesis. HDAC6 has been shown to be implicated in vascular remodeling. However, the role of airway HDAC6 signaling in pulmonary vascular remodeling in COPD and the underlying mechanisms remain undetermined. Here, we show that HDAC6 expression is upregulated in the lungs of patients with COPD and a COPD animal model. We also found that CS extract (CSE), PDGF, and IL-6 increase the protein levels and activation of HDAC6 in BSMCs and PASMCs. Furthermore, CSE and these stimulants induced deacetylation and phosphorylation of ERK1/2 and increased collagen synthesis and BSMC and PASMC proliferation, which were outcomes that were prevented by HDAC6 inhibition. Inhibition of ERK1/2 also diminished the CSE-, PDGF-, and IL-6-caused elevation in collagen levels and cell proliferation. Pharmacologic HDAC6 inhibition with tubastatin A prevented the CS-stimulated increases in the thickness of the bronchial and pulmonary arterial wall, airway resistance, emphysema, and right ventricular systolic pressure and right ventricular hypertrophy in a rat model of COPD. These data demonstrate that the upregulated HDAC6 governs the collagen synthesis and BSMC and PASMC proliferation that lead to airway and vascular remodeling in COPD.

Indexed as

Airway RemodelingMAP Kinase Signaling SystemVascular RemodelingAnimalsCytokinesDisease Models, AnimalHistone Deacetylase 6HumansHydroxamic AcidsIndolesMuscle, Smooth, VascularMyocytes, Smooth MusclePulmonary ArteryPulmonary Disease, Chronic ObstructiveRatsRats, Sprague-DawleyCytokinesHDAC6 protein, humanHDAC6 protein, ratHistone Deacetylase 6Hydroxamic AcidsIndolestubastatin Acigarette smokeCOPDHDAC6IL-6PDGF

Identifiers

PMID34280336
PMCPMC8641801
OpenAlexW3186838348

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.