Expression of Transforming Growth Factor β by Small Duct Epithelium in Chronic, Cancer-Associated, Obstructive Pancreatitis

Objectives Transforming growth factor beta (TGF-beta) is a dominant mediator of pancreatic fibrosis. The objective of this study was to identify cellular sources of TGF-beta mRNA and compare the results with previous immunohistochemical/in situ hybridization studies. Methods In situ hybridization of TGF-beta was conducted for 9 human tissues of chronic obstructive pancreatitis (COP) and 2 control specimens. By classifying these 9 COP tissues into 3 fibrosis phases by the amount of fibrotic space, histopathologic changes were examined for each fibrosis phase. Whether or not TGF-beta-positive cells were closely distributed to fibrosis was also investigated in control and COP cases. Results Three cases were categorized in early, intermediate, and advanced stages of fibrosis. Transforming growth factor beta mRNA was identified for a part of small duct epithelia, that is, intercalated ductule cells, centroacinar cells, and/or metaplastic ductal structures adjacent to acinar cells. The number of TGF-beta-positive cells was greater in COP cases than in controls. In controls and in the early stage of fibrosis, no fibrosis was seen near TGF-beta-positive cells. Conclusions Small duct epithelia are the main cellular sources of TGF-beta in COP, and many of them may be working for COP fibrosis either directly or indirectly.