Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy

Kohei Yasunaga, Tetsuhide Ito, Masami Miki, Keijiro Ueda, Takashi Fujiyama, Yuichi Tachibana, Nao Fujimori, Ken Kawabe, Yoshihiro Ogawa

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to "impaired autophagy flux". Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.

元の言語英語
記事番号8719397
ジャーナルBioMed Research International
2018
DOI
出版物ステータス出版済み - 1 1 2018

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Clustered Regularly Interspaced Short Palindromic Repeats
Acinar Cells
Autophagy
Amylases
Pancreatitis
Pancreatic Neoplasms
Ducts
Cells
Cell Survival
Fluxes
Inflammation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

これを引用

Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy. / Yasunaga, Kohei; Ito, Tetsuhide; Miki, Masami; Ueda, Keijiro; Fujiyama, Takashi; Tachibana, Yuichi; Fujimori, Nao; Kawabe, Ken; Ogawa, Yoshihiro.

:: BioMed Research International, 巻 2018, 8719397, 01.01.2018.

研究成果: ジャーナルへの寄稿記事

Yasunaga, Kohei ; Ito, Tetsuhide ; Miki, Masami ; Ueda, Keijiro ; Fujiyama, Takashi ; Tachibana, Yuichi ; Fujimori, Nao ; Kawabe, Ken ; Ogawa, Yoshihiro. / Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy. :: BioMed Research International. 2018 ; 巻 2018.
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