A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome.


Journal

Laboratory investigation; a journal of technical methods and pathology
ISSN: 1530-0307
Titre abrégé: Lab Invest
Pays: United States
ID NLM: 0376617

Informations de publication

Date de publication:
09 2020
Historique:
received: 25 08 2019
accepted: 19 04 2020
revised: 18 04 2020
pubmed: 6 5 2020
medline: 24 11 2020
entrez: 6 5 2020
Statut: ppublish

Résumé

Endoplasmic reticulum (ER) stress-mediated cell death is an emerging target for human chronic disorders, including neurodegeneration and diabetes. However, there is currently no treatment for preventing ER stress-mediated cell death. Here, we show that mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor secreted from ER stressed cells, prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome, a prototype of ER disorders. Our results indicate that molecular pathways regulated by MANF are promising therapeutic targets for regenerative therapy of ER stress-related disorders, including diabetes, retinal degeneration, neurodegeneration, and Wolfram syndrome.

Identifiants

pubmed: 32366942
doi: 10.1038/s41374-020-0436-1
pii: S0023-6837(22)00364-6
pmc: PMC7438202
mid: NIHMS1586015
doi:

Substances chimiques

MANF protein, mouse 0
Nerve Growth Factors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1197-1207

Subventions

Organisme : NCATS NIH HHS
ID : UH3 TR002065
Pays : United States
Organisme : NIDDK NIH HHS
ID : R21 DK113487
Pays : United States
Organisme : NIDDK NIH HHS
ID : F30 DK111070
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000448
Pays : United States
Organisme : NIDDK NIH HHS
ID : P60 DK020579
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020579
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112921
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NCATS NIH HHS
ID : UH2 TR002065
Pays : United States

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Auteurs

Jana Mahadevan (J)

Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Shuntaro Morikawa (S)

Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Takuya Yagi (T)

Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Damien Abreu (D)

Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Simin Lu (S)

Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Kohsuke Kanekura (K)

Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.

Cris M Brown (CM)

Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Fumihiko Urano (F)

Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA. urano@wustl.edu.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA. urano@wustl.edu.

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