High-mobility group box1 peptide ameliorates bronchopulmonary dysplasia (BPD) via suppressing inflammation and fibrosis in a mouse model.

Previously, we have shown that a synthesized peptide originated from high mobility group box-1 protein (HMGB1) induces a regenerative cascade via activating endogenous mesenchymal stem cells in the body. Here, we have tested whether the HMGB1 peptide can ameliorate BPD related manifestations. In a mouse BPD model established by hyperoxia exposure, three shots of the HMGB1 peptide significantly improved the survival and lung function. Single-cell RNA-seq analysis on the lung showed that an inflammatory signature in macrophages and a fibrotic signature in fibroblasts induced by hyperoxia exposure were significantly suppressed by the HMGB1 peptide. These changes in transcriptome were also confirmed at the protein level. Together, the HMGB1 peptide treatment prevented the progression of BPD by suppressing inflammation and fibrosis. Our data serve as a foundation to develop new effective therapies for BPD. Evaluation of responses to HMGB1 peptide in BPD mouse model at transcriptomic and molecular levels