Progenitor-Like Cells as an Etiological Factor and Potential Therapeutic Target in Alcohol-Induced Chronic Pancreatitis
Abstract
To examine the scientific hypothesis that disruption of ADM de-differentiation/ re-differentiation cycle induces hyper-sensitivity to chronic alcoholic pancreatitis and progenitor-like ADM cells can be targeted by the YAP1/TAZ pharmaceutical inhibitorVivace102 to improve chronic pancreatitis treatment, we propose to reconsider the etiological functions of progenitor-like ADM cells in chronic pancreatitis development from a new perspective and develop the new approach to cure chronic pancreatitis. In this reporting period, we finished the experiments to demonstrate that Vivace102 treatment could inhibit the pancreatic inflammation induced by YAP1/TAZ activation in pancreatic acinar cells. We also generated the new genetically modified mouse line and tested alcohol-dependent chronic pancreatitis induction in this line. We found that impairment of Hippo pathway in acinar cells increased the sensitivity of pancreas to alcohol treatment, but the incidence of alcohol-induced pancreatic fibrosis is still low. Our current data suggested that additional treatment to induce acute injury might help to establish a robust mouse model for alcohol-dependent chronic pancreatitis. We found that our genetically modified mice are sensitive to caerulein treatment-induced acute injury. We plan to incorporate caerulein treatment into our new chronic pancreatitis model in the next reporting period.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1190871
Entities
People
- Jun Liu
Organizations
- University of Texas at San Antonio