ArticleHeliyon2025
PPARG/SPP1/CD44 signaling pathway in alveolar macrophages: Mechanisms of lipid dysregulation and therapeutic targets in idiopathic pulmonary fibrosis.
Article in Heliyon, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Alveolar Macrophages: Development, Respiratory Homeostasis, Signal Pathways, Diseases, and Therapeutic Opportunities.MedComm · 2026Review
- The cortical microenvironment drives early immune organization and controls early osteoclastogenesis in bone healing.Nature communications · 2026Article
- Spatial transcriptomic analysis reveals spatial features in human Stanford type A aortic dissection.iScience · 2026Article
- An aerosolized dual-action autotaxin inhibitor-PPARγ agonist for the treatment of pulmonary fibrosis.Cell reports. Medicine · 2026Article
- The PPAR-gamma agonist pioglitazone alleviates bleomycin-induced lung fibrosis in male BALB/c mice.Multidisciplinary respiratory medicine · 2026Article
- The rise and fall of glucocorticoids and immunosuppressants in idiopathic pulmonary fibrosis: a historical paradigm shift driven by mechanistic understanding.Frontiers in immunology · 2026Review
- Integrated Network Pharmacology Analysis and Experimental Validation of Zadi-5 Against Coronary Heart Disease.Cardiology research and practice · 2026Article
- SPP1+ Macrophages Involved in Juvenile Xanthogranuloma via PPARG Signaling Pathway.Journal of inflammation research · 2026Article
- Pediatric exogenous lipoid pneumonia caused by paraffin oil aspiration: a case report.Frontiers in pediatrics · 2026Article
- CD44 as a Central Integrator of Inflammation and Fibrosis: From Molecular Signaling to Environmental Modulation.International journal of molecular sciences · 2025Review
- Article
- Deciphering the cellular and molecular landscape of cervical cancer progression through single-cell and spatial transcriptomics.NPJ precision oncology · 2025Article
- Ferroptosis-immune-metabolic axis in asthma: mechanistic crosstalk, endotype-specific regulation, and translational targeting.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. It is characterized by inflammation and fibrosis in the lung parenchyma and interstitium. Given its poor prognosis and limited treatment options, understanding the underlying molecular mechanisms is crucial. Recent evidence suggests that lipid metabolism plays a pivotal role in IPF pathogenesis, however, the precise mechanisms remain poorly understood. To address this, we analyzed 12 bulk RNA-seq and 2 single-cell RNA-seq datasets from the GEO database using machine learning approaches. As a result, we identified four key lipid-related genes-PPARG, SPP1, CASP3, and PECAM1-that are expressed across various cell types. Specifically, in alveolar macrophages (AMs), we observed that PPARG was significantly downregulated, while SPP1 was highly expressed. Importantly, PPARG serves as a transcriptional regulator of SPP1, which in turn mediates intercellular signaling via CD44. Based on these findings, we propose a novel PPARG/SPP1/CD44 signaling pathway in AMs, which modulates lipid metabolism and likely contributes to the progression of fibrosis in IPF. Moreover, network pharmacology analysis identified several herbal compounds that target PPARG, offering potential therapeutic opportunities. In conclusion, these findings highlight the critical role of lipid metabolism in IPF and present novel molecular targets for the development of future therapeutic strategies.
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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 Socratic graph.