Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells

Amani Al-Adsani, Zoe D Burke, Daniel Eberhard, Katherine L Lawrence, C N Shen, A K Rustgi, H Sakaue, J M Farrant, David Tosh

Research output: Contribution to journalArticle

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Abstract

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.

Methodology/Principal Findings: 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/EBP beta (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/EBP beta 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/EBP beta, liver inhibitory protein, inhibited hepatocyte formation in dexamethasone-treated cultures and enhanced the ductal phenotype.

Conclusions/Significance: 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/EBP beta.

LanguageEnglish
Article numbere13650
Number of pages12
JournalPLoS ONE
Volume5
Issue number10
DOIs
StatusPublished - 27 Oct 2010

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acinar cells
Acinar Cells
dexamethasone
Dexamethasone
hepatocytes
Hepatocytes
CCAAT-Enhancer-Binding Protein-beta
cells
Epidermal Growth Factor
epidermal growth factor
Cells
Keratin-7
Peanut Agglutinin
Keratin-19
Amylases
Transferrin
Phenotype
Liver
phenotype
Transcription Factors

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Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells. / Al-Adsani, Amani; Burke, Zoe D; Eberhard, Daniel; Lawrence, Katherine L; Shen, C N; Rustgi, A K; Sakaue, H; Farrant, J M; Tosh, David.

In: PLoS ONE, Vol. 5, No. 10, e13650, 27.10.2010.

Research output: Contribution to journalArticle

Al-Adsani, A, Burke, ZD, Eberhard, D, Lawrence, KL, Shen, CN, Rustgi, AK, Sakaue, H, Farrant, JM & Tosh, D 2010, 'Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells' PLoS ONE, vol 5, no. 10, e13650. DOI: 10.1371/journal.pone.0013650
Al-Adsani A, Burke ZD, Eberhard D, Lawrence KL, Shen CN, Rustgi AK et al. Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells. PLoS ONE. 2010 Oct 27;5(10). e13650. Available from, DOI: 10.1371/journal.pone.0013650
Al-Adsani, Amani ; Burke, Zoe D ; Eberhard, Daniel ; Lawrence, Katherine L ; Shen, C N ; Rustgi, A K ; Sakaue, H ; Farrant, J M ; Tosh, David. / Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells. In: PLoS ONE. 2010 ; Vol. 5, No. 10.
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