Platelet-Derived LGALS9 Suppresses NLRP3 Inflammasome-Dependent Pyroptosis in Pancreatic Acinar Cells During Severe Acute Pancreatitis.

BACKGROUND

Pyroptosis is a significant contributor to the development of severe acute pancreatitis (SAP), and the presence of SAP together with a reduced platelet count often indicates a poor prognosis. In this study, we screened targets from platelets and explored the role of lectin galactoside-binding soluble 9 (LGALS9) in acinar cell pyroptosis and inflammation in SAP.

METHODS

SAP cell models, alongside mouse models showing diminished platelet counts, were established using caerulein and lipopolysaccharide. We conducted transcriptomic sequencing on platelets from mice with and without SAP to identify possible targets, and we determined LGALS9 levels in platelet releasates and serum from both patients and mice with and without SAP. Bioinformatic analysis was then applied to predict the relationship between LGALS9 and pyroptosis-related proteins. Subsequently, recombinant LGALS9, α-lactose, and RG9-35 were used to treat SAP mice and acinar cells to evaluate the effect of LGALS9 on inflammation and its regulatory effects on acinar cell pyroptosis in SAP.

RESULTS

LGALS9 expression was upregulated in SAP platelets, and LGALS9 levels were found to be significantly elevated in platelet releasates and serum. Bioinformatic analysis illustrated the correlations and interactions between LGALS9 and the pyroptosis-related proteins ASC, NLRP3, caspase-1, and gasdermin D. Within the SAP context, LGALS9 may be potentially administered to diminish acinar cell pyroptosis-related protein levels, inhibit acinar cell pyroptosis, mitigate inflammatory factor levels, and alleviate pancreatic tissue inflammatory damage.

CONCLUSION

Our data indicated that LGALS9 expression was elevated in platelets of patients and mice with SAP. LGALS9 also inhibited NLRP3 inflammasome-dependent pyroptosis and suppressed inflammation in SAP.