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

Abstract 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....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hideaki Iwama, Sally Mehanna, Mai Imasaka, Shinsuke Hashidume, Hiroshi Nishiura, Ken-ichi Yamamura, Chigure Suzuki, Yasuo Uchiyama, Etsuro Hatano, Masaki Ohmuraya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7aa763c7ffb946598f69f406514abd4a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7aa763c7ffb946598f69f406514abd4a
record_format	dspace
spelling	oai:doaj.org-article:7aa763c7ffb946598f69f406514abd4a2021-12-02T14:02:55ZCathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis10.1038/s41598-021-85898-92045-2322https://doaj.org/article/7aa763c7ffb946598f69f406514abd4a2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85898-9https://doaj.org/toc/2045-2322Abstract 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.Hideaki IwamaSally MehannaMai ImasakaShinsuke HashidumeHiroshi NishiuraKen-ichi YamamuraChigure SuzukiYasuo UchiyamaEtsuro HatanoMasaki OhmurayaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hideaki Iwama Sally Mehanna Mai Imasaka Shinsuke Hashidume Hiroshi Nishiura Ken-ichi Yamamura Chigure Suzuki Yasuo Uchiyama Etsuro Hatano Masaki Ohmuraya Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis
description	Abstract 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.
format	article
author	Hideaki Iwama Sally Mehanna Mai Imasaka Shinsuke Hashidume Hiroshi Nishiura Ken-ichi Yamamura Chigure Suzuki Yasuo Uchiyama Etsuro Hatano Masaki Ohmuraya
author_facet	Hideaki Iwama Sally Mehanna Mai Imasaka Shinsuke Hashidume Hiroshi Nishiura Ken-ichi Yamamura Chigure Suzuki Yasuo Uchiyama Etsuro Hatano Masaki Ohmuraya
author_sort	Hideaki Iwama
title	Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis
title_short	Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis
title_full	Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis
title_fullStr	Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis
title_full_unstemmed	Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis
title_sort	cathepsin b and d deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7aa763c7ffb946598f69f406514abd4a
work_keys_str_mv	AT hideakiiwama cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT sallymehanna cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT maiimasaka cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT shinsukehashidume cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT hiroshinishiura cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT kenichiyamamura cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT chiguresuzuki cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT yasuouchiyama cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT etsurohatano cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis AT masakiohmuraya cathepsinbandddeficiencyinthemousepancreasinducesimpairedautophagyandchronicpancreatitis
_version_	1718392090099974144

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

Ejemplares similares