Evidence map›Paper›PMID 27064541›Full record

ArticleAmerican journal of respiratory cell and molecular biology2016

Knockout Mice Reveal a Major Role for Alveolar Epithelial Type I Cells in Alveolar Fluid Clearance.

Per Flodby, Yong Ho Kim, LaMonta L Beard, Danping Gao, Yanbin Ji, Hidenori Kage, Janice M Liebler, Parviz Minoo, Kwang-Jin Kim, Zea Borok and 1 more

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory cell and molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 18% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. Glycolytic activation of β-cell NaMolecular metabolism · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Remarkable sex-specific differences at single-cell resolution in neonatal hyperoxic lung injury.American journal of physiology. Lung cellular and molecular physiology · 2023
    Article
  15. Article
  16. Article
  17. Molecular mechanisms of Na,K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19.American journal of physiology. Lung cellular and molecular physiology · 2021
    Article
  18. Article
  19. Article
  20. Article
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

11 authors at 3 institutions in 1 country.

Per Flodby1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
Yong Ho Kim1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
LaMonta L Beard1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
Danping Gao1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
Yanbin Ji1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
Hidenori Kage1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
Janice M Liebler1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
Parviz Minoo2 Division of Neonatology, Department of Pediatrics, and.
Kwang-Jin Kim1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.ORCID 0000-0001-7547-1681
Zea Borok1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.ORCID 0000-0001-8673-8177
Edward D Crandall1 Will Rogers Institute Pulmonary Research Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
Rogers (United States) · USPediatrics and Genetics · USUniversity of Southern California · US

Funding

USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI OOKHTENS, MURAD · 1995 to 2020
$21.8M
MAPGen Knowledge Base (MAPGenKB) and Coordination CenterU01HL108634 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZHOU, XIANGHONG JASMINE · 2011 to 2015
$5.3M
PULMONARY DEVELOPMENT-- MOLECULAR &CELLULAR ANALYSISR01HL056590 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MINOO, PARVIZ MINOO · 1996 to 2012
$4.3M
Mechanisms of Lung Development and InjuryR01HL095349 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MINOO, PARVIZ MINOO · 2009 to 2017
$3.6M
Mechanisms of beta-catenin signaling in alveolar epithelial cell differentiationR01HL112638 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BOROK, ZEA, KAHN, MICHAEL · 2013 to 2016
$2.2M
Molecular programming of AEC differentiation: role of forkhead factorsR37HL062569 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BOROK, ZEA · 2010 to 2014
$2.2M
Nanoparticle properties and alveolar epithelial barrier/transport functionsR01ES017034 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRANDALL, EDWARD DAVID · 2009 to 2013
$1.8M
THE BIOLOGY OF PULMONARY ALVEOLAR FORMATIONR01HL122764 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MINOO, PARVIZ MINOO · 2015 to 2018
$1.6M
Role of claudin 18 in regulation of lung stem/progenitor cell homeostasisR01HL126877 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BOROK, ZEA · 2016 to 2017
$587k
Confocal Microscopy Imaging SystemS10RR022508 · NCRR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI OOKHTENS, MURAD · 2007 to 2007
$415k
NCRR NIH HHS S10 RR022508NHLBI NIH HHS R01 HL056590NHLBI NIH HHS R01 HL095349NHLBI NIH HHS R01 HL112638NHLBI NIH HHS R01 HL122764NHLBI NIH HHS R01 HL126877NHLBI NIH HHS R37 HL062569NHLBI NIH HHS U01 HL108634NIDDK NIH HHS P30 DK048522NIEHS NIH HHS R01 ES017034
6 · The paper itself

Abstract

Active ion transport by basolateral Na-K-ATPase (Na pump) creates an Na(+) gradient that drives fluid absorption across lung alveolar epithelium. The α1 and β1 subunits are the most highly expressed Na pump subunits in alveolar epithelial cells (AEC). The specific contribution of the β1 subunit and the relative contributions of alveolar epithelial type II (AT2) versus type I (AT1) cells to alveolar fluid clearance (AFC) were investigated using two cell type-specific mouse knockout lines in which the β1 subunit was knocked out in either AT1 cells or both AT1 and AT2 cells. AFC was markedly decreased in both knockout lines, revealing, we believe for the first time, that AT1 cells play a major role in AFC and providing insights into AEC-specific roles in alveolar homeostasis. AEC monolayers derived from knockout mice demonstrated decreased short-circuit current and active Na(+) absorption, consistent with in vivo observations. Neither hyperoxia nor ventilator-induced lung injury increased wet-to-dry lung weight ratios in knockout lungs relative to control lungs. Knockout mice showed increases in Na pump β3 subunit expression and β2-adrenergic receptor expression. These results demonstrate a crucial role for the Na pump β1 subunit in alveolar ion and fluid transport and indicate that both AT1 and AT2 cells make major contributions to these processes and to AFC. Furthermore, they support the feasibility of a general approach to altering alveolar epithelial function in a cell-specific manner that allows direct insights into AT1 versus AT2 cell-specific roles in the lung.

Indexed as

Absorption, PhysiologicalAlveolar Epithelial CellsAmilorideAnimalsBody FluidsGene TargetingHyperoxiaIon Channel GatingMice, KnockoutOrgan SizePermeabilityProtein SubunitsPulmonary EdemaReceptors, Adrenergic, beta-2Reproducibility of ResultsSodiumAmilorideAtp1b1 protein, mouseProtein SubunitsReceptors, Adrenergic, beta-2SodiumSodium ChannelsSodium-Potassium-Exchanging ATPaseTerbutalineion transportlungNa-K-ATPaseβ1 subunitβ2-adrenergic receptor

Identifiers

PMID27064541
PMCPMC5023030
OpenAlexW2314477558

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.