Related Experiment Video
Updated: Dec 17, 2025
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Blocking protein phosphatase 2A with a peptide protects mice against bleomycin-induced pulmonary fibrosis
Jun Yu1, Yuanjun Deng2, Min Han2
1Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Abstract:
Emerging data indicate that endothelial-mesenchymal transition (EndMT) is involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). A previous study noted that blocking the activity of protein phosphatase 2 A (PP2A) could attenuate EndMT. However, the treatment effects of PP2A inhibitors in pulmonary fibrosis remain not investigated. In the present study, we used a PP2A inhibitor, a newly designed peptide named TAT-Y127WT, to determine the role of PP2A in pulmonary fibrosis. Herein, we showed that TAT-Y127WT protected mice against BLM-induced pulmonary fibrosis by attenuating lung injury and fibrosis. Furthermore, a mechanistic study indicated that TAT-Y127WT could alleviate EndMT in the lungs following BLM induction. Overall, our data showed that PP2A might participate in pulmonary fibrogenesis by promoting EndMT, and TAT-Y127WT could be a potential candidate for new anti-fibrotic therapies for IPF patients.
Insights
A new study shows that blocking protein phosphatase 2A (PP2A) with TAT-Y127WT peptide can reduce lung injury and fibrosis in mice. This suggests PP2A inhibitors may offer new treatments for idiopathic pulmonary fibrosis (IPF).
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Pharmacology
Background:
- Idiopathic pulmonary fibrosis (IPF) pathogenesis involves endothelial-mesenchymal transition (EndMT).
- Protein phosphatase 2A (PP2A) activity blockade may attenuate EndMT.
- The therapeutic potential of PP2A inhibitors in pulmonary fibrosis is unexplored.
Purpose of the Study:
- To investigate the role of PP2A in pulmonary fibrosis.
- To evaluate the anti-fibrotic effects of a novel PP2A inhibitor, TAT-Y127WT.
Main Methods:
- Utilized a PP2A inhibitor, TAT-Y127WT, in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis.
- Assessed lung injury, fibrosis, and EndMT markers post-treatment.
Main Results:
- TAT-Y127WT administration protected mice against BLM-induced pulmonary fibrosis.
- The peptide treatment attenuated lung injury and fibrotic progression.
- Mechanistic studies revealed that TAT-Y127WT alleviated EndMT in the lungs.
Conclusions:
- PP2A appears to promote pulmonary fibrogenesis by enhancing EndMT.
- The PP2A inhibitor TAT-Y127WT demonstrates potential as a novel therapeutic agent for IPF.
