Regeneration and repair in the healing lung
Open accessAbstract
The lung achieves an efficient gas exchange between a complex non‐sterile atmosphere and the body via a delicate and extensive epithelial surface, with high efficiency because of elastic deformation allowing for an increase and decrease in volume during the process of breathing and because of an extensive vasculature which aids rapid gas diffusion. The lungs’ large surface area exposes the organ to a continual risk of damage from pathogens, toxins or irritants; however, lung damage can be rapidly healed via regenerative processes that restore its structure and function. In response to sustained and extensive damage, the lung is healed via a non‐regenerative process resulting in scar tissue which locally stiffens its structure, which over time leads to a serious loss of lung function and to increasing morbidities. This review discusses what is known about the factors which influence whether a lung is healed by regeneration or repair and what potential new therapeutic approaches may positively influence lung healing.
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Excessive and persistent damage to alveolar architecture often precedes dysregulated tissue repair processes and fibrosis.
“The observed loss of alveolar basement membrane integrity indicates excessive and persistent damage to the alveolar architecture, which often precedes dysregulated tissue repair processes and fibrosis (16, 17).”
From Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 (2021) · cites this paper as [17]
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D’Agnillo, F., Walters, K.-A., Xiao, Y., Sheng, Z.-M., Scherler, K., Park, J., Gygli, S., Rosas, L. A., Sadtler, K., Kalish, H., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abj7790 · Cited by 237 · see citing works
Future therapies for cystic fibrosis
Allen, L., Allen, L. J., Carr, S. B., Davies, G., Downey, D. G., Egan, M. E., Forton, J. T., Gray, R. D., HAWORTH, C. S., Horsley, A. R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36244-2 · Cited by 143 · see citing works
New Insights into Hippo/YAP Signaling in Fibrotic Diseases
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Raslan, A., Pham, T. X., Lee, J., Kontodimas, K., Tilston-Lünel, A., Schmottlach, J., Hong, J., Dinc, M. T., Bujor, A. M., Caporarello, N., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49545-x · Cited by 79 · see citing works
Mia, M. M., & Singh, M. K. (2022) · FEBS Journal · doi:10.1111/febs.16449 · Cited by 46 · see citing works
Jana, S., Heaven, M. R., Stauft, C. B., Wang, T. T., Williams, M. C., D’Agnillo, F., & Alayash, A. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010558 · Cited by 33 · see citing works
The disruptive role of LRG1 on the vasculature and perivascular microenvironment
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Auld, S. C., Sheshadri, A., Alexander‐Brett, J. M., Aschner, Y., Barczak, A. K., Basil, M. C., Cohen, K. A., Cruz, C. S. D., McGroder, C. F., Restrepo, M. I., et al. (2024) · Annals of the American Thoracic Society · doi:10.1513/annalsats.202406-651st · Cited by 27 · see citing works
Silva, K. D., Kumar, P., & Choonara, Y. E. (2025) · Wound Repair and Regeneration · doi:10.1111/wrr.13251 · Cited by 30 · see citing works
Bellio, M. A., Bennett, C., Arango, A., Khan, A., Xu, X., Barrera, C. I. E., Friedewald, V. E., & Mitrani, M. I. (2021) · Biomaterials and Biosystems · doi:10.1016/j.bbiosy.2021.100031 · Cited by 22 · see citing works
Sideratou, C.-M., & Papaneophytou, C. P. (2023) · Infectious Disease Reports · doi:10.3390/idr15060072 · Cited by 22 · see citing works
Pereverzeva, L., Uhel, F., Sengers, H. P., Cremer, O. L., Schultz, M. J., Bonten, M. J. M., Scicluna, B. P., & van der Poll, T. (2021) · Annals of Intensive Care · doi:10.1186/s13613-021-00930-5 · Cited by 13 · see citing works
Butt, S. P., Kakar, V., Abdulaziz, S., Razzaq, N., Saleem, Y., Kumar, A., Ashiq, F., Ghisulal, P. K., Thrush, A., Malik, S. J., et al. (2024) · Journal of ExtraCorporeal Technology · doi:10.1051/ject/2024023 · Cited by 13 · see citing works
Promising use of immune cell‐derived exosomes in the treatment of SARS‐CoV‐2 infections
Alahdal, M., & Elkord, E. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.1026 · Cited by 12 · see citing works
Medicinal Mushrooms and Their Use to Strengthen Respiratory Health during and Post-COVID-19 Pandemic
Booi, H.-N., Lee, M.-K., Fung, S. Y., Ng, S. T., Tan, C.-S., Lim, K., Roberts, R. E., & Ting, K. (2022) · International journal of medicinal mushrooms · doi:10.1615/intjmedmushrooms.2022045068 · Cited by 10 · see citing works
Persistent alveolar type 2 dysfunction and lung structural derangement in post-acute COVID-19Preprint
Rendeiro, A. F., Ravichandran, H., Kim, J., Borczuk, A., Elemento, O., & Schwartz, R. E. (2022) · medRxiv · doi:10.1101/2022.11.28.22282811 · Cited by 9 · see citing works
Cancer treatments as paradoxical catalysts of tumor awakening in the lung
Nicolas, É., Kośmider, B., Cukierman, E., Borghaei, H., Golemis, E. A., & Borriello, L. (2024) · Cancer and Metastasis Reviews · doi:10.1007/s10555-024-10196-5 · Cited by 7 · see citing works
Alveolar Regeneration in COVID-19 Patients: A Network Perspective
Gupta, S. K., Srivastava, M., Minocha, R., Akash, A., Dangwal, S., & Dandekar, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011279 · Cited by 7 · see citing works
Nanoparticle-Based Inhalation Therapy for Pulmonary Diseases
Yadav, D., Wairagu, P. M., Kwak, M., & Jin, J.-O. (2022) · Current Drug Metabolism · doi:10.2174/1389200223666220803103039 · Cited by 7 · see citing works
Mizuno, Y., Watanabe, S., Katano, M., Yanagihara, T., Maki, N., Sato, Y., & Taguchi, T. (2021) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37339 · Cited by 6 · see citing works
Granulomatous cellular signatures in nontuberculous and tuberculous mycobacterial infections
Doratt, B. M., Napier, E. G., Boroujeni, M. E., Douglas, S., Davies, M. H., Bermudez, L. E., Spindel, E. R., McCaffrey, E., & Messaoudi, I. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1741883 · Cited by 4 · see citing works
Immunopathobiology of chronic lung disease
Prêle, C. M., & Hoyne, G. F. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1170 · Cited by 2 · see citing works
Does ‘sub-threshold’ ventilatory stress promote healing after lung injury?
Marini, J. J., Kummer, R. L., & Rocco, P. R. M. (2024) · Intensive Care Medicine Experimental · doi:10.1186/s40635-024-00644-5 · Cited by 1 · see citing works
Use of the Wnt/β-catenin Activator Lithium Is Associated with Less Emphysema
Chandra, D., Allbright, K., Kinney, G. L., Li, Y., Bowler, R., Serban, K. A., Nouraie, S. M., Nyunoya, T., Dutta, P., Rennard, S. I., et al. (2026) · Annals of the American Thoracic Society · doi:10.1093/annalsats/aaoag167 · Cited by 1 · see citing works
Zieba, J. T., Bagheri, R., Kot, A., Martin, J. H., Wachtell, D., Wong, S., Mungovan, M., Wight, C., & Krakow, D. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2026.1713393 · Cited by 1 · see citing works
Zheng, X., Wang, L., Hu, L., Guo, X., Lv, M., Wu, N., Chen, J., Xiao, H., Zhang, H., & Zhou, D. (2026) · Advanced Functional Materials · doi:10.1002/adfm.75611 · Cited by 1 · see citing works
Kočan, L., Firment, J., Pirníková, I., Iannaccone, S. F., Rybár, D., Gnoriková, J., Korcek, J., Kočanová, H., Török, P., Rapčanová, S., et al. (2023) · Medicine · doi:10.1097/md.0000000000033052 · Cited by 1 · see citing works
On The Functional Dynamics of Alveolar and Ductal Growth in The Adolescent LungPreprint
Moats, R. A., Koos, D. S., Shi, W., Tang, Y. H., Pollack, H. A., Tipre, D. N., Khuu, T., Larionov, V., Wigfall, C. M., Tawhai, M. H., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-632711/v1
Influence of Changes in Functional Residual Capacity on EIT Imaging in Spontaneous Breathing
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A Comparative Analysis of Aging Across Causes of Death
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- Authors
- Lucas, A., Yasa, J., & Lucas, M.
- Affiliations
- The University of Western Australia (AU)
- Corresponding author
- Lucas, Andrew
- Venue
- Clinical & Translational Immunology
- Publisher
- Wiley
- Published
- 2020-01
- Volume
- 9
- Issue
- 7
- Pages
- e1152-e1152
- ISSN
- 2050-0068 (ISSN-L)
- PMC
- PMC7338595
- OpenAlex
- W3041891204
- Cited by
- 41
- References
- 93
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 7 · 2021: 12 · 2020: 1
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Clinical & Translational Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Murdoch University Research Portal (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Murdoch University
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- lung regeneration, lung repair, lung injury, scar formation, pulmonary fibrosis, lung epithelium, lung function
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.
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