Wnt/β-catenin signalling plays diverse functions during the process of fibrotic remodelling in the exocrine pancreas

Wnt/β-catenin signalling plays vital roles in tissue homeostasis. Dysregulation of the pathway has been implicated in the pathogenesis of cancer and fibroses in numerous tissues, including the pancreas. We studied the effect of microenvironmental changes pertaining to fibrotic tissue remodelling on the expression of selected Wnt/β-catenin pathway proteins in the human exocrine pancreas. The role of acinar/stellate cross-talk on the expression of the proteins was elucidated in a long-term mouse co-culture system. Expression of β-catenin, Wnt2, Wnt5a and SFRP4 was analysed immunohistochemically in normal and moderately or highly fibrotic human pancreata (n = 8). The effect of humoral interactions on the expression of the proteins was studied by immunocytochemical means in parallel mono- and co-cultures of mouse acinar and stellate cells (PSCs). In human pancreatic tissue, fibrotic microenvironment was associated with redistribution of the proteins in and between epithelial and stromal compartments, compared to acinar-rich tissue. In non-fibrotic and moderately fibrotic tissue the proteins appeared only in acinar cells whereas in highly fibrotic tissue stromal fibroblastoid/stellate cells and macrophages were their predominant locations. Subcellular changes in the expression of β-catenin and Wnt5a were detected. Our in vitro data suggest potential involvement of acinar cell/PSC cross-talk in mediating the changes observed in tissue specimens. Wnt/β-catenin pathway-associated proteins are abundantly expressed in the exocrine pancreas with prominent changes in their cellular and subcellular expression patterns along with increasing levels of fibrosis. Diverse functions for Wnt/β-catenin signalling during the course of fibrotic remodelling in the exocrine pancreas are suggested.