RNA sequence analysis reveals pathways and candidate genes associated with pancreatic acinar cells injury in a mouse pancreatitis model

Compared with acute pancreatitis caused by other reasons, hyperlipidemia pancreatitis has a higher severity, complication and organ failure rate. Our previous studies have found that hyperglycemia may promote the occurrence and development of hyperlipidemia pancreatitis, but the mechanism is still unclear. Pancreatic acinar cell injury is the initial link of acute pancreatitis and plays a vital role in the course of the disease. The aim of the present study was to analyze the differentially expressed genes (DEGs) between hyperlipidemia acute pancreatitis (HLAP) mouse and hyperglycemia and hyperlipidemia acute pancreatitis (HLGAP) mouse by RNA-sequence. The GO and KEGG analysis of these DEGs did not indicate a direct pathway related to acinar cell injury. However, in further targeted analysis, we found that there are different genes related to cell injury between the HLAP and HLGAP groups, such as necroptosis, autophagy, mitophagy and ferroptosis. In the later immunofluorescence experiments, it was also confirmed that the genes related to cell injury were significantly differentially expressed between the two groups. In conclusion, there are multiple cell injury modes in the course of hyperglycemia and hyperlipidemia pancreatitis. More importantly, the correlation and transition between multiple cell injury modes may be the key mechanism for the occurrence and development of pancreatitis.