PAI-1 Inhibitor TM5441 Attenuates Emphysema and Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease
Abstract
1. Introduction
2. Results
2.1. Effects of Intratracheal Administration of CSE on Emphysema
2.2. CSE-Induced Lung Functional Impairment
2.3. Effects of CSE on Total Cell, Macrophage, and Neutrophil Counts in the Bronchoalveolar Lavage Fluid (BALF)
2.4. Effects of CSE on PAI-1 Expression in Lung Tissues and PAI-1 Activity in Plasma
2.5. Effects of TM5441 on CSE-Induced Pulmonary Emphysema
2.6. Effects of TM5441 on CSE-Induced Respiratory Dysfunction
2.7. Effects of TM5441 on CSE-Induced Inflammatory Cell Infiltration in BALF
2.8. Effects of TM5441 on CSE-Induced PAI-1 Expression in Lung Tissue and Plasma PAI-1 Activity
2.9. Effects of TM5441 on CSE-Induced NE mRNA Expression and Protein Levels in Lung Tissue
2.10. Effects of TM5441 on Coagulation Parameters
3. Discussion
4. Materials and Methods
4.1. Animals and Experimental Protocol
4.2. Preparation of CSE
4.3. Intratracheal CSE-Induced COPD Model
4.4. TM5441 Administration
4.5. Histopathological Analysis
4.6. Lung Physiology and BAL
4.7. RT-PCR
4.8. ELISA
4.9. Coagulation Times
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BALF | Bronchoalveolar lavage fluid |
Cdyn | Dynamic compliance |
COPD | Chronic obstructive pulmonary disease |
CSE | Cigarette smoke extract |
DI | Destructive index |
FITC | Fluorescein isothiocyanate |
FSC | Forward scatter |
Gr-1 | Ly-6G/Ly-6C |
HE | Hematoxylin and eosin |
L-NAME | Nω-nitro-arginine methyl ester |
MLI | Mean linear intercept |
NE | Neutrophil elastase |
PAI-1 | Plasminogen activator inhibitor-1 |
PE | Phycoerythrin |
RI | Airway resistance |
SSC | Side scatter |
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Oishi, K.; Yasui, H.; Inoue, Y.; Hozumi, H.; Suzuki, Y.; Karayama, M.; Furuhashi, K.; Enomoto, N.; Fujisawa, T.; Horinouchi, T.; et al. PAI-1 Inhibitor TM5441 Attenuates Emphysema and Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease. Int. J. Mol. Sci. 2025, 26, 7086. https://doi.org/10.3390/ijms26157086
Oishi K, Yasui H, Inoue Y, Hozumi H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Horinouchi T, et al. PAI-1 Inhibitor TM5441 Attenuates Emphysema and Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease. International Journal of Molecular Sciences. 2025; 26(15):7086. https://doi.org/10.3390/ijms26157086
Chicago/Turabian StyleOishi, Kyohei, Hideki Yasui, Yusuke Inoue, Hironao Hozumi, Yuzo Suzuki, Masato Karayama, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Takahiro Horinouchi, and et al. 2025. "PAI-1 Inhibitor TM5441 Attenuates Emphysema and Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease" International Journal of Molecular Sciences 26, no. 15: 7086. https://doi.org/10.3390/ijms26157086
APA StyleOishi, K., Yasui, H., Inoue, Y., Hozumi, H., Suzuki, Y., Karayama, M., Furuhashi, K., Enomoto, N., Fujisawa, T., Horinouchi, T., Iwaki, T., Suzuki, Y., Miyata, T., Inui, N., & Suda, T. (2025). PAI-1 Inhibitor TM5441 Attenuates Emphysema and Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease. International Journal of Molecular Sciences, 26(15), 7086. https://doi.org/10.3390/ijms26157086