"Biliary obstruction and cholangiocyte hyperproliferation are important features of diseases affecting bile ducts, while the mechanisms driving bile duct cell responses to injury are understudied. We employed complementary approaches with in vivo model of biliary obstruction in mice, in vitro models of proliferating (bile duct organoids) and quiescent (bile duct explants) cholangiocytes and transcriptomic analyses. We found that WNT signaling upregulation plays an important role in the cholangiocyte proliferative response to bile duct obstruction, and that cholangiocytes are the primary source and target of WNT signaling utilizing β-catenin-dependent mechanism to promote biliary proliferation. Our studies inform strategies for the modulation of bile duct repair and control of maladaptive biliary hyperproliferation."
Pictured second from left: Dr. Nataliya Razumilava, M.D. (Assistant Professor, Internal Medicine, University of Michigan) with members of her lab.