ArticleDisease models & mechanisms2019
Adenosine and hyaluronan promote lung fibrosis and pulmonary hypertension in combined pulmonary fibrosis and emphysema.
Article in Disease models & mechanisms, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- An increased risk of pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema: a meta-analysis.BMC pulmonary medicine · 2023Pooled it
- Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension.Thorax · 2025Trial
- Oral hymecromone decreases hyaluronan in human study participants.The Journal of clinical investigation · 2022Trial
- Adipocyte-specific deletion of sine oculis homeobox homolog 1 inhibits lipolysis and reduces skin fibrosis.JCI insight · 2026Article
- Plasma proteomic and machine learning models for differentiating idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease: findings from a prospective cohort.Respiratory research · 2026Article
- Article
- Decoding fibrosis in nonresolvable COVID-19: a role for myeloid-specific HIF1A deletion.American journal of physiology. Cell physiology · 2025Article
- Does Adenosine Triphosphate via Purinergic Receptor Signalling Fuel Pulmonary Fibrosis?Journal of innate immunity · 2025Review
- Pulmonary hypertension in the setting of interstitial lung disease: Approach to management and treatment. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative-Group 3 Pulmonary Hypertension.Pulmonary circulation · 2024Review
- The vascular perspective on acute and chronic lung disease.The Journal of clinical investigation · 2023Review
- Probiotic-Derived Ecto-5'-Nucleotidase Produces Anti-Inflammatory Adenosine Metabolites in Treg-Deficient Scurfy Mice.Probiotics and antimicrobial proteins · 2023Article
- Hyaluronan synthesis inhibition normalizes ethanol-enhanced hepatic stellate cell activation.Alcohol, clinical & experimental research · 2023Article
- Review
- Probiotic-derived ecto-5'-nucleotidase produces anti-inflammatory adenosine metabolites in Treg-deficient scurfy mice.Research square · 2023Article
- A2B Adenosine Receptor in Idiopathic Pulmonary Fibrosis: Pursuing Proper Pit Stop to Interfere with Disease Progression.International journal of molecular sciences · 2023Review
- Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- 4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing.International journal of molecular sciences · 2023Article
- Chitinase 3 like 1 contributes to the development of pulmonary vascular remodeling in pulmonary hypertension.JCI insight · 2022Article
- 3'UTR shortening of HAS2 promotes hyaluronan hyper-synthesis and bioenergetic dysfunction in pulmonary hypertension.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Biochemical, biophysical, and immunological characterization of respiratory secretions in severe SARS-CoV-2 infections.JCI insight · 2022Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that predominantly affects male smokers or ex-smokers and it has a mortality rate of 55% and a median survival of 5 years. Pulmonary hypertension (PH) is a frequently fatal complication of CPFE. Despite this dismal prognosis, no curative therapies exist for patients with CPFE outside of lung transplantation and no therapies are recommended to treat PH. This highlights the need to develop novel treatment approaches for CPFE. Studies from our group have demonstrated that both adenosine and its receptor ADORA2B are elevated in chronic lung diseases. Activation of ADORA2B leads to elevated levels of hyaluronan synthases (HAS) and increased hyaluronan, a glycosaminoglycan that contributes to chronic lung injury. We hypothesize that ADORA2B and hyaluronan contribute to CPFE. Using isolated CPFE lung tissue, we characterized expression levels of ADORA2B and HAS. Next, using a unique mouse model of experimental lung injury that replicates features of CPFE, namely airspace enlargement, PH and fibrotic deposition, we investigated whether 4MU, a HAS inhibitor, was able to inhibit features of CPFE. Increased protein levels of ADORA2B and HAS3 were detected in CPFE and in our experimental model of CPFE. Treatment with 4MU was able to attenuate PH and fibrosis but not airspace enlargement. This was accompanied by a reduction of HAS3-positive macrophages. We have generated pre-clinical data demonstrating the capacity of 4MU, an FDA-approved drug, to attenuate features of CPFE in an experimental model of chronic lung injury.This article has an associated First Person interview with the first author of the paper.
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Registered trials
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.