Administration of the HMGB1 fragment suppresses expression of collagen-related genes

To analyze cell profiles in pancreatic tissue, single-cell RNA-seq of CD45-negative cells was performed using pancreatic tissue obtained in the eighth week after HMGB1 fragment injection was begun. After conventional quality check and filtering, we recovered pancreas cells from normal pancreas, control group pancreas, and HMGB1 group pancreas. The UMAP plots depicted 11 distinct cell clusters from the three groups, PDGFRα＋ cells had the most significant number of clusters, which exhibited a high level of Col1α1 gene expression in the bubble plot.Compared with the control and HMGB1 groups, the distribution of the PDGFRα＋ cell cluster was skewed in the normal group. We focused on PDGFRα＋ cell clusters that secrete large amounts of collagen and extracellular matrix components, which are central to the pathogenesis of CP. Many genes were significantly expressed in contrasting ways, gene clusters that were upregulated in the control compared with the normal group were downregulated in the HMGB1 compared with the control group. In contrast, gene groups that were downregulated in the control compared with the normal group were upregulated in the HMGB1 compared with the control group. HMGB1 fragment exposure was associated with a shift in the gene expression pattern of CP toward that of the normal pancreas. Expression of Ccn2 and Ccn1 was upregulated in the control group compared with the normal group but downregulated in the HMGB1 group compared with the control group. Pten expression was downregulated in the control versus normal group but upregulated in the HMGB1 group compared with the controls. Extracellular matrix–related genes in the pancreas were altered with HMGB1 fragment administration.