Pexidartinib and Nintedanib Combination Therapy Targets Macrophage Polarization to Reverse Pulmonary Fibrosis: A Preclinical Study
Abstract
1. Introduction
2. Results
2.1. Enhanced Efficacy of Nintedanib in RIPF Through Combined Treatment with PLX3397
2.2. Effect of the PLX3397 and Nintedanib Combination Therapy on Macrophage Polarization During RIPF Development
2.3. Modulation of Macrophage Polarization-Mediated Vascular Effects in RIPF
2.4. Synergistic Effects of Nintedanib and PLX3397 in Restoring BIPF and Prolonging Survival
2.5. Effects of M1/M2 Macrophage Polarization on Vascularization During BIPF
2.6. Cell-Level Characteristics of Patients with IPF Analyzed Using Single-Cell RNA Sequencing Data
3. Discussion
4. Materials and Methods
4.1. Mice and Ethical Approval
4.2. RIPF Model
4.3. Bleomycin-Induced PF (BIPF Model)
4.4. Immunohistochemistry and Immunofluorescence Staining
4.5. Microcone Beam CT (Micro-CBCT)
4.6. Cell Culture and Tube Formation Assay
4.7. Single-Cell RNA Sequencing Data Analysis
4.8. Antibodies for Immunofluorescence and Immunohistochemistry Staining
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Kim, J.-H.; Nam, J.-K.; Park, M.-S.; Seo, S.; Ryu, H.C.; Lee, H.-J.; Lee, J.; Lee, Y.-J. Pexidartinib and Nintedanib Combination Therapy Targets Macrophage Polarization to Reverse Pulmonary Fibrosis: A Preclinical Study. Int. J. Mol. Sci. 2025, 26, 7570. https://doi.org/10.3390/ijms26157570
Kim J-H, Nam J-K, Park M-S, Seo S, Ryu HC, Lee H-J, Lee J, Lee Y-J. Pexidartinib and Nintedanib Combination Therapy Targets Macrophage Polarization to Reverse Pulmonary Fibrosis: A Preclinical Study. International Journal of Molecular Sciences. 2025; 26(15):7570. https://doi.org/10.3390/ijms26157570
Chicago/Turabian StyleKim, Ji-Hee, Jae-Kyung Nam, Min-Sik Park, Seungyoul Seo, Hyung Chul Ryu, Hae-June Lee, Jeeyong Lee, and Yoon-Jin Lee. 2025. "Pexidartinib and Nintedanib Combination Therapy Targets Macrophage Polarization to Reverse Pulmonary Fibrosis: A Preclinical Study" International Journal of Molecular Sciences 26, no. 15: 7570. https://doi.org/10.3390/ijms26157570
APA StyleKim, J.-H., Nam, J.-K., Park, M.-S., Seo, S., Ryu, H. C., Lee, H.-J., Lee, J., & Lee, Y.-J. (2025). Pexidartinib and Nintedanib Combination Therapy Targets Macrophage Polarization to Reverse Pulmonary Fibrosis: A Preclinical Study. International Journal of Molecular Sciences, 26(15), 7570. https://doi.org/10.3390/ijms26157570