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Publication : Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis.

First Author  Iwama H Year  2021
Journal  Sci Rep Volume  11
Issue  1 Pages  6596
PubMed ID  33758261 Mgi Jnum  J:304924
Mgi Id  MGI:6695599 Doi  10.1038/s41598-021-85898-9
Citation  Iwama H, et al. (2021) Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis. Sci Rep 11(1):6596
abstractText  The major lysosomal proteases, Cathepsin B (CTSB), Cathepsin D (CTSD) and Cathepsin L (CTSL), are implicated in autophagic activity. To investigate the role of each cathepsin in the exocrine pancreas, we generated mice in which the pancreas was specifically deficient in Ctsb, Ctsd and Ctsl. Each of these gene knockout (KO) and Ctsb;Ctsl and Ctsd;Ctsl double-knockout (DKO) mice were almost normal. However, we found cytoplasmic degeneration in the pancreatic acinar cells of Ctsb;Ctsd DKO mice, similar to autophagy related 5 (Atg5) KO mice. LC3 and p62 (autophagy markers) showed remarkable accumulation and the numbers of autophagosomes and autolysosomes were increased in the pancreatic acinar cells of Ctsb;Ctsd DKO mice. Moreover, these Ctsb;Ctsd DKO mice also developed chronic pancreatitis (CP). Thus, we conclude that both Ctsb and Ctsd deficiency caused impaired autophagy in the pancreatic acinar cells, and induced CP in mice.
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