Abstract
Background: Increasing evidence has linked the Hippo pathway with the fibroinflammatory diseases. However, the detailed roles of key hippo components in pancreatic inflammatory diseases still remain unclear. Methods: A series of genetic knockout mice were generated targeting the key components of Hippo pathway to examine the individual effects of YAP1 and TAZ on pancreatic inflammation. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence staining were performed to evaluate the pancreas tissue from mice with various genotypes. The therapeutic potential of a recently developed YAP1/TAZ inhibitor VT-104 was also evaluated in our mouse model. Results: Mice with acinar-specific knockout of YAP1/TAZ did not exhibit any histological abnormalities in the pancreas. LATS1/2 deficiency induced acinar to ductal metaplasia, immune cell infiltration, and fibroblast activation, which were rescued by the homozygous knockout YAP1, but not TAZ. Additionally, treatment with VT-104 also decreased pathological alterations induced by deletions of LATS1 and LATS2 in acinar cells. Conclusion: Our findings highlight the critical role of YAP1 in modulating pancreatic inflammation and demonstrate that VT-104 holds therapeutic potential to mitigate pancreatitis-associated pathological manifestations. Further exploration is necessary to unravel the underlying mechanisms and translate these insights into clinical applications.
Original language | English (US) |
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Pages (from-to) | 32-40 |
Number of pages | 9 |
Journal | Journal of Pancreatology |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - Mar 1 2025 |
Keywords
- Fibrosis
- Hippo pathway
- Inflammation
- Pancreatitis
- TAP1/TAZ
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Hepatology
- Endocrinology