ArticleProceedings of the National Academy of Sciences of the United States of America2021
LRRK2 plays essential roles in maintaining lung homeostasis and preventing the development of pulmonary fibrosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial.Nature medicine · 2026Trial
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- Article
- Atg5 deficiency alters myofibroblast accumulation and alveolar regeneration in lung fibrosis.Stem cell reports · 2026Article
- Convergent Microenvironment Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Expert reviews in molecular medicine · 2026Review
- The structural basis for LRRK2's activation and autoinhibition.bioRxiv : the preprint server for biology · 2026Article
- Alveolar macrophage-neutrophil crosstalk in acute lung injury: mechanisms, feedback loops, and therapeutic opportunities.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Prenatal diisononyl phthalate exposure induces the development of pulmonary dysplasia in offspring.Scientific reports · 2026Article
- FGFR signaling establishes spatial gradients of secretory cell identities along the airway proximal-distal axis.Nature communications · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Refractory Lung Diseases: From Cellular Structures, Molecular Mechanisms to Therapeutic Strategies.Pediatric discovery · 2026Review
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Single-nucleus RNA sequencing reveals the distinct heterogeneity of primary pulmonary sarcomas (PPS) and pulmonary sarcomatoid carcinoma (PSC).Clinical and translational medicine · 2026Article
- Peroxiredoxin 4 as a switch regulating PTEN/AKT axis in alveolar macrophages activation.Signal transduction and targeted therapy · 2025Article
- GPR40 activation alleviates pulmonary fibrosis by repressing M2 macrophage polarization through the PKD1/CD36/TGF-β1 pathway.Acta pharmacologica Sinica · 2025Article
- SLC34A2 inhibits tumorigenesis and progression via upregulating LRRK2/TTF-1/SELENBP1 axis in lung adenocarcinoma.Cancer gene therapy · 2025Article
- Article
- The role of autophagy in fibrosis: Mechanisms, progression and therapeutic potential (Review).International journal of molecular medicine · 2025Review
- YAP as a potential therapeutic target for myofibroblast formation in asthma.Respiratory research · 2025Article
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perturbation of lung homeostasis is frequently associated with progressive and fatal respiratory diseases, such as pulmonary fibrosis. Leucine-rich repeat kinase 2 (LRRK2) is highly expressed in healthy lungs, but its functions in lung homeostasis and diseases remain elusive. Herein, we showed that LRRK2 expression was clearly reduced in mammalian fibrotic lungs, and LRRK2-deficient mice exhibited aggravated bleomycin-induced pulmonary fibrosis. Furthermore, we demonstrated that in bleomycin-treated mice, LRRK2 expression was dramatically decreased in alveolar type II epithelial (AT2) cells, and its deficiency resulted in profound dysfunction of AT2 cells, characterized by impaired autophagy and accelerated cellular senescence. Additionally, LRRK2-deficient AT2 cells showed a higher capacity of recruiting profibrotic macrophages via the CCL2/CCR2 signaling, leading to extensive macrophage-associated profibrotic responses and progressive pulmonary fibrosis. Taken together, our study demonstrates that LRRK2 plays a crucial role in preventing AT2 cell dysfunction and orchestrating the innate immune responses to protect against pulmonary fibrosis.
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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.