Zoledronic acid targets the mevalonate pathway causing reduced cell recruitment and attenuation of pulmonary fibrosis
Tanner, L.; Bergwik, J.; Bhongir, R. K. V.; Egesten, A.
Show abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreparable scarring of lung tissue, resulting in most patients succumbing rapidly after diagnosis. With limited treatment options available, repurposing of current pharmaceuticals offers an expeditious option to address this dire need. The mevalonate pathway, which is involved in the regulation of cell proliferation, survival and motility, is targeted by the bisphosphonate zoledronic acid (ZA). In this study, administration of ZA reduced myofibroblast transition and blocked NF-kB signaling in macrophages leading to impaired immune cell recruitment. ZA treatment of mice with bleomycin-induced lung damage displayed decreased levels of cytokines in the BALF, plasma, and lung tissue, resulting in less histologically visible fibrotic scarring. Additionally, bleomycin induced production of the ZA target, farnesyl diphosphate synthase (FDPS), was reduced in lung tissue and fibroblasts upon ZA treatment. Therefore, ZA administration offers an expedient and efficacious treatment option against IPF in a clinical setting. TeaserRepurposing of zoledronic acid potentially offers a clinically viable treatment for idiopathic pulmonary fibrosis
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Pharmacological Inhibition of Epac1 Protects against Pulmonary Fibrosis by Blocking FoxO3a Neddylation 94%
- Acute Respiratory Distress Syndrome is associated with impaired alveolar macrophage efferocytosis 93%
- Resolving phenotypic and prognostic differences in interstitial lung disease related to systemic sclerosis by computed tomography-based radiomics 93%
Similar papers in this journal
- Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice 97%
- High-Throughput Analysis of Lung Immune Cells in a Murine Model of Rheumatoid Arthritis-Associated Lung Disease 95%
- HDAC6 inhibitor ACY-1083 shows lung epithelial protective features in COPD 95%
Similar papers in this journal
- Kasugamycin is a novel chitinase 1 inhibitor with strong antifibrotic effects on pulmonary fibrosis 96%
- Bortezomib inhibits lung fibrosis and fibroblast activation without proteasome inhibition 96%
- FK506-binding protein 13 expression is upregulated in interstitial lung disease and correlated with clinical severity: a potentially protective role. 95%
Similar papers in this journal
- Inhibiting endothelial cell Mst1 attenuates acute lung injury in mice 94%
- Essential Role of Protein Kinase R in the Pathogenesis of Pulmonary Veno-occlusive Disease 94%
- Inhibition of histone readers bromodomain extra-terminal proteins alleviates skin fibrosis in experimental models of scleroderma 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.