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Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation

2006; Cold Spring Harbor Laboratory Press; Volume: 20; Issue: 11 Linguagem: Inglês

10.1101/gad.1412806

1549-5477

Takeshi Miyatsuka, Hideaki Kaneto, Toshihiko Shiraiwa, Taka‐aki Matsuoka, Kaoru Yamamoto, Ken Kato, Yumiko Nakamura, Shizuo Akira, Kiyoshi Takeda, Yoshitaka Kajimoto, Yoshimitsu Yamasaki, Eric P. Sandgren, Yoshiya Kawaguchi, Christopher V.E. Wright, Yoshio Fujitani,

Diabetes and associated disorders

The transcription factor pancreatic and duodenal homeobox factor 1 (PDX-1) is expressed in pancreatic progenitor cells. In exocrine pancreas, PDX-1 is down-regulated during late development, while re-up-regulation of PDX-1 has been reported in pancreatic cancer and pancreatitis. To determine whether sustained expression of PDX-1 could affect pancreas development, PDX-1 was constitutively expressed in all pancreatic lineages by transgenic approaches. The transgenic pancreas was markedly small with the replacement of acinar cells by duct-like structures, accompanied by activated Stat3. Genetic ablation of Stat3 in the transgenic pancreas profoundly suppressed the metaplastic phenotype. These results provide a mechanism of pancreatic metaplasia by which persistent PDX-1 expression cell-autonomously induces acinar-to-ductal transition through Stat3 activation.