Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation
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 pancre...
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| Materiálatiipa: | Journal Article |
| Giella: | English |
| Almmustuhtton: |
2018
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| Liŋkkat: | https://hdl.handle.net/10356/88611 http://hdl.handle.net/10220/46945 |
| _version_ | 1826111877638258688 |
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| author | Valdez, Ivan Achel Dirice, Ercument Gupta, Manoj K. Shirakawa, Jun Teo, Adrian Kee Keong Kulkarni, Rohit N. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Valdez, Ivan Achel Dirice, Ercument Gupta, Manoj K. Shirakawa, Jun Teo, Adrian Kee Keong Kulkarni, Rohit N. |
| author_sort | Valdez, Ivan Achel |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T02:57:45Z |
| format | Journal Article |
| id | ntu-10356/88611 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:57:45Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/886112023-02-28T17:02:40Z Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation Valdez, Ivan Achel Dirice, Ercument Gupta, Manoj K. Shirakawa, Jun Teo, Adrian Kee Keong Kulkarni, Rohit N. School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Biological sciences Cytokines Pancreatic Ducts 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. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2018-12-13T06:21:06Z 2019-12-06T17:07:14Z 2018-12-13T06:21:06Z 2019-12-06T17:07:14Z 2016 Journal Article 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 2211-1247 https://hdl.handle.net/10356/88611 http://hdl.handle.net/10220/46945 10.1016/j.celrep.2016.03.036 27068459 en Cell Reports © 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/). 20 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Cytokines Pancreatic Ducts Valdez, Ivan Achel Dirice, Ercument Gupta, Manoj K. Shirakawa, Jun Teo, Adrian Kee Keong Kulkarni, Rohit N. Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation |
| title | Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation |
| title_full | Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation |
| title_fullStr | Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation |
| title_full_unstemmed | Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation |
| title_short | Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation |
| title_sort | proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via stat3 dependent ngn3 activation |
| topic | DRNTU::Science::Biological sciences Cytokines Pancreatic Ducts |
| url | https://hdl.handle.net/10356/88611 http://hdl.handle.net/10220/46945 |
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