Abstract

Pancreatic adenocarcinoma (PDAC) andchronic pancreatitis (CP) are characterized by a desmoplastic reactioninvolving activated pancreatic stellate cells (PSCs). However, the mechanismsof PSC activation remain poorly understood. We examined whether theepithelial-mesenchymal transition (EMT) process might play a role in PSCactivation. PSCs were isolated from a rat pancreas and characterized using immunofluorescenceand immunocytochemistry. We evaluated changes in cell motility and in theexpression levels of a panel of EMT-related genes during the PSC activationprocess. Activation of PSCs occurred after 48 h of in vitro culture, asindicated by a morphological change to a myofibroblastic shape and a decreasein the number of cytoplasmic lipid droplets. After activation, PSCs showedenhanced cell migration ability compared to quiescent cells. In addition, theexpression of epithelial markers (E-cadherin, BMP7 and desmoplakin) decreased,while expression of mesenchymal markers (N-cadherin, vimentin, fibronectin1,collagen1α1 and S100A4) increased in activated PSCs. EMT-related transcriptionfactors (Snail and Slug) were also upregulated after PSC activation. Theconcurrent increase in cell migration ability and alterations in EMT-relatedgene expression suggests that the activation of PSCs involves an EMT-likeprocess. The knowledge that PSC activation involves an EMT‑like process may help to identify potential new therapeutic targetsto alleviate pancreatic fibrosis in diseases like CP and PDAC.