Blocking protein phosphatase 2A with a peptide protects mice against bleomycin-induced pulmonary fibrosis.

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.