Evidence map›Paper›PMID 20395557›Full record

Trial reportAmerican journal of respiratory and critical care medicine2010

Inhibition and role of let-7d in idiopathic pulmonary fibrosis.

Kusum V Pandit, David Corcoran, Hanadie Yousef, Manohar Yarlagadda, Argyris Tzouvelekis, Kevin F Gibson, Kazuhisa Konishi, Samuel A Yousem, Mandal Singh, Daniel Handley and 10 more

Open access · greenAbstract readClinical Trial
In one paragraph

Trial report in American journal of respiratory and critical care medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 295 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
295citing papers in PubMed, 2 pooled it
27.4field-weighted citation impact, top 1% 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

295 citing papers in PubMed, 2 syntheses or guidelines pooled it, 499 citations in OpenAlex.

  1. Pooled it
  2. A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2017
    Pooled it
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026
    Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Inhalable Hsa-miR-30a-3p Liposomes Attenuate Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  19. Article
  20. Article

235 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

20 authors at 5 institutions in 4 countries.

Kusum V PanditUniversity of Pittsburgh Medical Center, NW 628 MUH, 3459 5th Avenue, Pittsburgh, PA 15261, USA. kaminskin@upmc.edu
David Corcoran
Hanadie Yousef
Manohar Yarlagadda
Argyris Tzouvelekis
Kevin F Gibson
Kazuhisa Konishi
Samuel A Yousem
Mandal Singh
Daniel Handley
Thomas Richards
Moises Selman
Simon C Watkins
Annie Pardo
Ahmi Ben-Yehudah
Demosthenes Bouros
Oliver Eickelberg
Prabir Ray
Panayiotis V Benos
Naftali Kaminski
University of Pittsburgh · USDemocritus University of Thrace · GRInstitut für Urheber- und Medienrecht · DEInstituto Nacional de Enfermedades Respiratorias · MXUniversidad Nacional Autónoma de México · MX

Funding

Lung Genomics Research ConsortiumRC2HL101715 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI GERACI, MARK W, KAMINSKI, NAFTALI · 2009 to 2010
$11.4M
New Molecular Targets in Pulmonary FibrosisR01HL073745 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMINSKI, NAFTALI · 2003 to 2006
$2.8M
Modeling in vivo Protein-DNA Interactions from High-Throughput Data MP1/1R01LM009657 · NLM · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BENOS, PANAGIOTIS V, KAMINSKI, NAFTALI · 2007 to 2011
$2.5M
NHLBI NIH HHS HL073745NHLBI NIH HHS HL0894932NHLBI NIH HHS RC2HL101715NLM NIH HHS LM009657NLM NIH HHS R01 LM009657
6 · The paper itself

Abstract

rationaleIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually lethal fibrotic lung disease characterized by profound changes in epithelial cell phenotype and fibroblast proliferation.

objectivesTo determine changes in expression and role of microRNAs in IPF.

methodsRNA from 10 control and 10 IPF tissues was hybridized on Agilent microRNA microarrays and results were confirmed by quantitative real-time polymerase chain reaction and in situ hybridization. SMAD3 binding to the let-7d promoter was confirmed by chromatin immunoprecipitation, electrophoretic mobility shift assay, luciferase assays, and reduced expression of let-7d in response to transforming growth factor-beta. HMGA2, a let-7d target, was localized by immunohistochemistry. In mice, let-7d was inhibited by intratracheal administration of a let-7d antagomir and its effects were determined by immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, and morphometry. MEASUREMENTS AND MAIN

resultsEighteen microRNAs including let-7d were significantly decreased in IPF. Transforming growth factor-beta down-regulated let-7d expression, and SMAD3 binding to the let-7d promoter was demonstrated. Inhibition of let-7d caused increases in mesenchymal markers N-cadherin-2, vimentin, and alpha-smooth muscle actin (ACTA2) as well as HMGA2 in multiple epithelial cell lines. let-7d was significantly reduced in IPF lungs and the number of epithelial cells expressing let-7d correlated with pulmonary functions. HMGA2 was increased in alveolar epithelial cells of IPF lungs. let-7d inhibition in vivo caused alveolar septal thickening and increases in collagen, ACTA2, and S100A4 expression in SFTPC (pulmonary-associated surfactant protein C) expressing alveolar epithelial cells.

conclusionsOur results indicate a role for microRNAs in IPF. The down-regulation of let-7d in IPF and the profibrotic effects of this down-regulation in vitro and in vivo suggest a key regulatory role for this microRNA in preventing lung fibrosis. Clinical trial registered with www.clinicaltrials.gov (NCT 00258544).

Indexed as

ActinsAnimalsCadherinsCells, CulturedDown-RegulationEpithelial CellsHMGA2 ProteinHumansIdiopathic Pulmonary FibrosisIn Situ HybridizationLungMiceMice, Inbred C57BLMicroRNAsPolymerase Chain ReactionPulmonary AlveoliACTA2 protein, humanActinsCadherinsHMGA2 ProteinMicroRNAsmirnlet7 microRNA, humanS100a4 protein, mouseS100 Calcium-Binding Protein A4S100 ProteinsSmad3 ProteinTransforming Growth Factor betaVimentin

Identifiers

PMID20395557
PMCPMC2913236
OpenAlexW2009001235

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.