Metalloproteinase inhibitors regulate biliary progenitor cells through sDLK1 in organoid models of liver injury.

ABSTRACT: Understanding cell fate regulation in the liver is necessary to advance cell therapies for hepatic disease. Liver progenitor cells (LPCs) contribute to tissue regeneration after severe hepatic injury, yet signals instructing progenitor cell dynamics and fate are largely unknown. Tissue inhibitor of metalloproteinases 1 (TIMP1) and TIMP3 control the sheddases ADAM10 and ADAM17, key for NOTCH activation. Here we uncover the role of the TIMP/ADAM/NOTCH/DLK1 axis in LPC maintenance and cholangiocyte specification. Combined TIMP1/TIMP3 loss in vivo caused abnormal portal triad stoichiometry accompanied by collagen deposits, dysregulated Notch signaling, and increased soluble DLK1. The MIC1-1C3+CD133+CD26- biliary progenitor population was reduced following acute CCl4 or chronic DDC liver injury

SUBMITTER: Defamie V 

PROVIDER: S-EPMC11785925 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature