Cited by 134Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisMetabolism, Diabetes, and CancerCancer, Hypoxia, and Metabolism

Glucose Transporter 1–Dependent Glycolysis Is Increased during Aging-Related Lung Fibrosis, and Phloretin Inhibits Lung Fibrosis

Open access
Cho, Soo Jung, Moon, Jong-Seok, Lee, Chang-Min, Choi, Augustine M. K., Stout-Delgado, Heather W.·2017·American Journal of Respiratory Cell and Molecular Biology

Abstract

Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer, and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage, and reactive oxygen species generation. Although glycolysis has been linked to cell growth and proliferation, the mechanisms by which the activation of glycolysis by aging regulates fibrogenesis in the lung remain unclear. The objective of this study was to determine if glucose transporter 1 (GLUT1)–induced glycolysis regulates age-dependent fibrogenesis of the lung. Mouse and human lung tissues were analyzed for GLUT1 and glycolytic markers using immunoblotting. Glycolytic function was measured using a Seahorse apparatus. To study the effect of GLUT1, genetic inhibition of GLUT1 was performed by short hairpin RNA transduction, and phloretin was used for pharmacologic inhibition of GLUT1. GLUT1-dependent glycolysis is activated in aged lung. Genetic and pharmacologic inhibition of GLUT1 suppressed the protein expression of α-smooth muscle actin, a key cytoskeletal component of activated fibroblasts, in mouse primary lung fibroblast cells. Moreover, we demonstrated that the activation of AMP-activated protein kinase, which is regulated by GLUT1-dependent glycolysis, represents a critical metabolic pathway for fibroblast activation. Furthermore, we demonstrated that phloretin, a potent inhibitor of GLUT1, significantly inhibited bleomycin-induced lung fibrosis in vivo. These results suggest that GLUT1-dependent glycolysis regulates fibrogenesis in aged lung and that inhibition of GLUT1 provides a potential target of therapy of age-related lung fibrosis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1165/rcmb.2016-0225oc

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Aged fibroblasts have augmented glucose utilization and increased resistance to apoptosis, which may underlie increased susceptibility of the aged lung to fibrogenesis.

    “Specifically, aged fibroblasts have augmented glucose utilization and increased resistance to apoptosis, which may underlie increased susceptibility of the aged lung to fibrogenesis (144).”

    From Aging and Lung Disease (2020) · cites this paper as [144]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

2 retracted

Flagged first, then by citations

Research works printed but not linked: 2

  1. [4]4. Wynn TA, Ramalingam TR. Mechanisms of fi brosis: therapeutic translation for fi brotic disease. Nat Med 2012;18:1028 -1040.
  2. [7]7. Xie N, Tan Z, Banerjee S, Cui H, Ge J, Liu RM, Bernard K, Thannickal VJ, Liu G. Glycolytic reprogramming in myo fi broblast differentiation and lung fi brosis. Am J Respir Crit Care Med 2015;192:1462 -1474.

Cited by

Sorted by citations

Authors
Cho, S. J., Moon, J.-S., Lee, C.-M., Choi, A. M. K., & Stout-Delgado, H. W.
Affiliations
  • NewYork–Presbyterian Hospital (US)
  • Brown University (US)
Corresponding author
Stout-Delgado, Heather W.
Venue
American Journal of Respiratory Cell and Molecular Biology
Published
2017-04-01
Volume
56
Issue
4
Pages
521-531
ISSN
  • 1044-1549 (ISSN-L)
  • 1535-4989
OpenAlex
W2576471964
Cited by
133
References
46
Citations by year
2026: 14 · 2025: 11 · 2024: 17 · 2023: 16 · 2022: 14 · 2021: 24 · 2020: 17 · 2019: 11 · 2018: 6 · 2017: 3
FWCI
8.37
Type
journal article
Language
en
Open access
Locations
  • American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (L30 AG043118, R21AG044755, K01AG034999)
  • National Heart, Lung, and Blood Institute (P01HL114501)
  • National Institute of Allergy and Infectious Diseases (T32AI007613)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
glucose transporter 1, GLUT1, glycolysis, pulmonary fibrosis, aging, phloretin, AMPK, fibroblast activation, alpha-smooth muscle actin, bleomycin-induced fibrosis, metabolic reprogramming, therapeutic target
MeSH terms
Aging, Animals, Bleomycin, Enzyme Activation, Glycolysis, Male, Mice, Inbred C57BL, Phloretin, Phosphorylation, Pulmonary Fibrosis, Cellular Senescence, Glucose Transporter Type 1, AMP-Activated Protein Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review