Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation.
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.
Miyatsuka
Takeshi
T
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Kaneto
Hideaki
H
Shiraiwa
Toshihiko
T
Matsuoka
Taka-aki
TA
Yamamoto
Kaoru
K
Kato
Ken
K
Nakamura
Yumiko
Y
Akira
Shizuo
S
Takeda
Kiyoshi
K
Kajimoto
Yoshitaka
Y
Yamasaki
Yoshimitsu
Y
Sandgren
Eric P
EP
Kawaguchi
Yoshiya
Y
Wright
Christopher V E
CV
Fujitani
Yoshio
Y
D000818:Animals; D018398:Homeodomain Proteins / Q000235:genetics*; D008679:Metaplasia; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics*
D018398:Homeodomain Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein