Cellular and Molecular Mechanisms of Idiopathic Pulmonary Fibrosis

A Special Issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1162

Editors


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Guest Editor
Department of Biochemistry and Molecular Biology, Severance Medical Research Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
Interests: molecular biology; lung disease; drug discovery; research mechanism in respiratory disease

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Guest Editor
1. Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
2. Toronto General Hospital Research Institute, University Health Network, 101 College Street PMCRT 2-814, Toronto, ON M5G 1L7, Canada
Interests: acute lung injury; lung transplantation; drug discovery; nano-drug formulation; signal transduction; cell biology; thyroid function

Special Issue Information

Dear Colleagues,

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant epithelial repair, fibroblast activation, immune dysregulation, and excessive extracellular matrix deposition. Although recent studies have advanced our understanding of IPF, the molecular and cellular mechanisms underlying disease initiation and progression remain incompletely defined, and effective therapeutic options are still limited.

This Special Issue, entitled “Cellular and Molecular Mechanisms of Idiopathic Pulmonary Fibrosis”, will provide a comprehensive platform to explore the fundamental biology of IPF within the scope of Cells. We invite submissions focusing on the pathways and processes regulating epithelial–mesenchymal crosstalk, immune and inflammatory responses, genetic and epigenetic regulation, metabolic reprogramming, cellular senescence, autophagy, and extracellular matrix remodeling. Both mechanistic studies and integrative approaches that identify novel biomarkers, therapeutic targets, or innovative models are welcome.

In this Special Issue, original research articles and reviews are encouraged. Research areas may include, but are not limited to, cellular and molecular signaling, disease modeling, and translational strategies that deepen our understanding of IPF biology. We look forward to receiving your contributions.

Dr. Sooyeon Lee
Prof. Dr. Mingyao Liu
Guest Editors

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Keywords

  • idiopathic pulmonary fibrosis
  • fibroblast activation
  • epithelial–mesenchymal interaction
  • extracellular matrix remodeling
  • inflammation
  • signaling pathways
  • biomarkers
  • molecular targets
  • autophagy
  • senescence

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Published Papers (1 paper)

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Research

21 pages, 15177 KB  
Article
Stepwise Translational Validation of the Screening Hit Desipramine Reveals Limits of Fibroblast-State Modulation in Lung Fibrosis
by Georgios-Dimitrios Panagiotidis, Stefano Rivetti, Manuela Marega, Afshin Noori, Elie El Agha, Malgorzata Wygrecka, Peter Braubach, Raffaella Klima, Luca Braga and Saverio Bellusci
Cells 2026, 15(15), 1344; https://doi.org/10.3390/cells15151344 - 27 Jul 2026
Viewed by 541
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options. Depression and anxiety are common comorbidities in patients with IPF, and emerging evidence suggests that neuroactive pathways may also influence fibrotic remodeling. On this basis, we investigated [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options. Depression and anxiety are common comorbidities in patients with IPF, and emerging evidence suggests that neuroactive pathways may also influence fibrotic remodeling. On this basis, we investigated desipramine, a tricyclic antidepressant, as a potential modulator of fibroblast state in lung fibrosis. Desipramine was identified in an FDA-approved compound screen as a pro-lipogenic hit in TGF-β-stimulated fibroblasts and was subsequently evaluated across a stepwise validation pipeline of increasing biological complexity. In WI-38 fibroblasts, desipramine was well tolerated at 10 μM and reduced myofibroblast-associated features while increasing lipid-associated staining. In a fibroblast-supported alveolosphere assay, desipramine altered qualitative organoid clustering and changed the transcript levels of specific mesenchymal markers under profibrotic stimulation, whereas direct treatment of MLE-12 epithelial cells did not elicit a consistent response. While desipramine demonstrated pro-lipogenic and anti-myofibroblastic phenotypic shifts in reductionist 2D cultures, these effects failed to translate robustly into complex 3D human lung tissue slices or in vivo disease models. Ultimately, our findings highlight the critical necessity of utilizing complex translational pipelines to rigorously validate early screening hits before therapeutic efficacy is assumed. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Idiopathic Pulmonary Fibrosis)
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