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

Abstract Bronchopulmonary dysplasia (BPD) is a chronic lung disorder that affect approximately 40% of preterm infants, with no established curative therapy. The administration of mesenchymal stem cells (MSCs) to BPD patients has shown promising outcomes. Previously, we demonstrated that a synthesized peptide originating from high mobility group box-1 protein (HMGB1) induces a regenerative cascade through activating endogenous MSCs. Here, we tested whether the HMGB1 peptide can ameliorate BPD-related lung injury. In a mouse BPD model established via hyperoxia exposure, three shots of HMGB1 peptide significantly improved survival and suppressed inflammation and fibrosis in the lung. Single-cell RNA-sequencing of the lung further showed that the peptide significantly suppressed a hyperoxia-induced inflammatory signature in macrophages and fibrotic signature in fibroblasts. These changes in the transcriptome were also confirmed at the protein level. Taken together, our data show that treatment with the HMGB1 peptide suppressed inflammation and fibrosis, thus preventing BPD progression. This study serves as a foundation for the development of new effective therapies for BPD.