Non-canonical Wnt Signalling Regulates Scarring in Biliary Disease via the Planar Cell Polarity Receptors

Chronic bile duct disease can cause liver scarring and, in some cases, result in the need for liver transplantation. The scarring process can be damaging to the liver, but the cells involved in scarring also play a role in healing and regenerating the liver.

Embryonic mesothelial-derived hepatic lineage of quiescent and heterogenous scar-orchestrating cells defined but suppressed by WT1.

Activated hepatic stellate cells orchestrate scarring during liver injury. Here we define morphologically and transcriptionally discreet subpopulations of aHSCs.

Non-canonical Wnt signalling initiates scarring in biliary disease

Using human tissue, bile duct organoids and animal models of biliary disease, we show that non-canonical Wnt signalling is important in initiating biliary scarring.

WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited.

These results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for Cholangiocarcinoma.

Inhibition of JAK-STAT signaling stimulates adult satellite cell function.

This work shows age-related intrinsic properties that functionally distinguish satellite cells and suggest a promising therapeutic avenue for the treatment of muscle-wasting diseases.