Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/88611
Title: Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation
Authors: Valdez, Ivan Achel
Dirice, Ercument
Gupta, Manoj K.
Shirakawa, Jun
Teo, Adrian Kee Keong
Kulkarni, Rohit N.
Keywords: DRNTU::Science::Biological sciences
Cytokines
Pancreatic Ducts
Issue Date: 2016
Source: Valdez, I. A., Dirice, E., Gupta, M. K., Shirakawa, J., Teo, A. K. K., & Kulkarni, R. N. (2016). Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation. Cell Reports, 15(3), 460-470. doi:10.1016/j.celrep.2016.03.036
Series/Report no.: Cell Reports
Abstract: A major goal of diabetes research is to develop strategies that replenish pancreatic insulin-producing beta cells. One emerging strategy is to harness pancreatic plasticity—the ability of pancreatic cells to undergo cellular interconversions—a phenomenon implicated in physiological stress and pancreatic injury. Here, we investigate the effects of inflammatory cytokine stress on the differentiation potential of ductal cells in a human cell line, in mouse ductal cells by pancreatic intraductal injection, and during the progression of autoimmune diabetes in the non-obese diabetic (NOD) mouse model. We find that inflammatory cytokine insults stimulate epithelial-to-mesenchymal transition (EMT) as well as the endocrine program in human pancreatic ductal cells via STAT3-dependent NGN3 activation. Furthermore, we show that inflammatory cytokines activate ductal-to-endocrine cell reprogramming in vivo independent of hyperglycemic stress. Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration.
URI: https://hdl.handle.net/10356/88611
http://hdl.handle.net/10220/46945
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.03.036
Schools: School of Biological Sciences 
Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2016 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
SBS Journal Articles

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