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Induced Mist1 expression promotes remodeling of mouse pancreatic acinar cells.

Abstract：

BACKGROUND & AIMS:Early embryogenesis involves cell fate decisions that define the body axes and establish pools of progenitor cells. Development does not stop once lineages are specified; cells continue to undergo specific maturation events, and changes in gene expression patterns lead to their unique physiological functions. Secretory pancreatic acinar cells mature postnatally to synthesize large amounts of protein, polarize, and communicate with other cells. The transcription factor MIST1 is expressed by only secretory cells and regulates maturation events. MIST1-deficient acinar cells in mice do not establish apical-basal polarity, properly position zymogen granules, or communicate with adjacent cells, disrupting pancreatic function. We investigated whether MIST1 directly induces and maintains the mature phenotype of acinar cells. METHODS:We analyzed the effects of Cre-mediated expression of Mist1 in adult Mist1-deficient (Mist1(KO)) mice. Pancreatic tissues were collected and analyzed by light and electron microscopy, immunohistochemistry, real-time polymerase chain reaction analysis, and chromatin immunoprecipitation. Primary acini were isolated from mice and analyzed in amylase secretion assays. RESULTS:Induced expression of Mist1 in adult Mist1(KO) mice restored wild-type gene expression patterns in acinar cells. The acinar cells changed phenotypes, establishing apical-basal polarity, increasing the size of zymogen granules, reorganizing the cytoskeletal network, communicating intercellularly (by synthesizing gap junctions), and undergoing exocytosis. CONCLUSIONS:The exocrine pancreas of adult mice can be remodeled by re-expression of the transcription factor MIST1. MIST1 regulates acinar cell maturation and might be used to repair damaged pancreata in patients with pancreatic disorders.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Direnzo D,Hess DA,Damsz B,Hallett JE,Marshall B,Goswami C,Liu Y,Deering T,Macdonald RJ,Konieczny SF

doi

10.1053/j.gastro.2012.04.011

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

469-80

issue

2

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(12)00561-6

journal_volume

143

pub_type

杂志文章

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