Autophagy impairment in pancreatic acinar cells causes zymogen granule accumulation and pancreatitis

被引：21

作者：

Iwahashi, Kiyoshi ^{[1
]}

Hikita, Hayato ^{[1
]}

Makino, Yuki ^{[1
]}

Shigekawa, Minoru ^{[1
]}

Ikezawa, Kenji ^{[1
]}

Yoshioka, Teppei ^{[1
]}

Kodama, Takahiro ^{[1
]}

Sakamori, Ryotaro ^{[1
]}

Tatsumi, Tomohide ^{[1
]}

Takehara, Tetsuo ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, 2Yamada Oka, Suita, Osaka 5650871, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2018年 / 503卷 / 04期

关键词：

Autophagy; Pancreas; Zymogen granule; Pancreatitis; Chronic pancreatitis; Atg7; TRYPSINOGEN ACTIVATION; BASAL AUTOPHAGY; PATHOGENESIS; PROTECTS; RELEASE; MICE;

D O I：

10.1016/j.bbrc.2018.07.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Basal autophagy degrades many kinds of proteins and organelles to maintain quality and plays important roles in cellular homeostasis. However, the impact of basal autophagy on zymogen granules in pancreatic acinar cells is unknown. In the present study, we examined the influence of autophagy impairment in acinar cells on zymogen granules and homeostasis of the pancreas, using mice with pancreas-specific autophagy impairment (Pdx1-Cre(+/-) Atg7(fl/fl) mice). The number of zymogen granules in acinar cells from these mice did not differ from that in acinar cells from their wild-type littermates at 3 weeks of age. However, the number of zymogen granules in acinar cells drastically increased at 4 weeks of age in mice with pancreas-specific autophagy impairment. In addition to the increased number of zymogen granules, serum lipase was elevated, and the pancreas became oedematous at 4 weeks of age, suggesting pancreatitis. After 5 weeks of age, acinar cell death was accelerated, and several histological features of chronic pancreatitis were observed, including glandular atrophy and pseudotubular complexes with fibrotic changes. In conclusion, the impairment of pancreas-specific basal autophagy caused spontaneous zymogen granule accumulation in acinar cells and pancreatitis, which eventually led to chronic pancreatitis. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：2576 / 2582

页数：7

共 33 条

[1] STUDIES ON DISPERSED PANCREATIC EXOCRINE CELLS .1. DISSOCIATION TECHNIQUE AND MORPHOLOGIC CHARACTERISTICS OF SEPARATED CELLS [J].