Mst1 participates in the progression of severe acute pancreatitis-induced intestinal barrier dysfunction via inhibiting autophagy and enhancing apoptosis.

Abstract

Objective: Severe acute pancreatitis (SAP) is a common emergency condition associated with high mortality. Intestinal barrier dysfunction plays a critical role in the pathogenesis of SAP. Mammalian sterile 20-like kinase 1 (Mst1) has been shown to coordinately regulate autophagy and apoptosis in cardiac and aging-related diseases. However, the precise role of Mst1 in SAP-induced intestinal barrier dysfunction remains largely unknown. This study aimed to investigate the pathophysiological impact of Mst1 on SAP-induced intestinal barrier dysfunction.

Methods: Mst1-knockout and wild-type mice were challenged intraperitoneally with caerulein combined with lipopolysaccharide (LPS) to establish an experimental SAP model. TNF-α-stimulated MODE-K cells were used to analyze the impact on autophagy and apoptosis and to elucidate the underlying mechanisms.

Results: Mst1 knockout up-regulated tight junction proteins, alleviated apoptosis and enhanced autophagy in the ileocolic mucosa tissue of SAP mice, which consequently improved cumulative survival and alleviated intestinal barrier dysfunction. Conversely, Mst1 overexpression inhibited autophagy and promoted apoptosis in TNF-α-stimulated MODE-K cells.

Conclusion: Mst1 plays an important role in SAP-related intestinal barrier dysfunction by inhibiting autophagy and enhancing apoptosis.