Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells.
BACKGROUND
The pancreatic exocrine cell line AR42J-B13 can be reprogrammed to hepatocytes following treatment with dexamethasone. The question arises whether dexamethasone also has the capacity to induce ductal cells as well as hepatocytes.


RESULTS
AR42J-B13 cells were treated with and without dexamethasone and analyzed for the expression of pancreatic exocrine, hepatocyte and ductal markers. Addition of dexamethasone inhibited pancreatic amylase expression, induced expression of the hepatocyte marker transferrin as well as markers typical of ductal cells: cytokeratin 7 and 19 and the lectin peanut agglutinin. However, the number of ductal cells was low compared to hepatocytes. The proportion of ductal cells was enhanced by culture with dexamethasone and epidermal growth factor (EGF). We established several features of the mechanism underlying the transdifferentiation of pancreatic exocrine cells to ductal cells. Using a CK19 promoter reporter, we show that a proportion of the ductal cells arise from differentiated pancreatic exocrine-like cells. We also examined whether C/EBPβ (a transcription factor important in the conversion of pancreatic cells to hepatocytes) could alter the conversion from acinar cells to a ductal phenotype. Overexpression of an activated form of C/EBPβ in dexamethasone/EGF-treated cells provoked the expression of hepatocyte markers and inhibited the expression of ductal markers. Conversely, ectopic expression of a dominant-negative form of C/EBPβ, liver inhibitory protein, inhibited hepatocyte formation in dexamethasone-treated cultures and enhanced the ductal phenotype.


CONCLUSIONS
These results indicate that hepatocytes and ductal cells may be induced from pancreatic exocrine AR42J-B13 cells following treatment with dexamethasone. The conversion from pancreatic to hepatocyte or ductal cells is dependent upon the expression of C/EBPβ.
Department of Biology and Biochemistry, Centre for Regenerative Medicine, University of Bath, Bath, United Kingdom.
Amani
A
Al-Adsani
Zoë D
ZD
Burke
Daniel
D
Eberhard
Katherine L
KL
Lawrence
Chia-Ning
CN
Shen
Anil K
AK
Rustgi
Hiroshi
H
Sakaue
J Mark
JM
Farrant
David
D
Tosh
D000818:Animals; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D002461:Cell Line, Transformed; D003907:Dexamethasone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005434:Flow Cytometry; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D022782:CCAAT-Enhancer-Binding Protein-beta; C545014:Cebpb protein, rat; D004815:Epidermal Growth Factor; D003907:Dexamethasone