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Role of cystatin C in amyloid precursor protein-induced proliferation of neural stem/progenitor cells
journal contribution
posted on 2023-05-17, 18:29 authored by Hu, Y, Hung, AC, Cui, H, Dawkins, E, Bolos, M, Lisa FoaLisa Foa, Kaylene YoungKaylene Young, David SmallDavid SmallThe amyloid precursor protein (APP) is well studied for its role in Alzheimer's disease. However, little is known about its normal function. In this study, we examined the role of APP in neural stem/progenitor cell (NSPC) proliferation. NSPCs derived from APP-overexpressing Tg2576 transgenic mice proliferated more rapidly than NSPCs from the corresponding background strain (C57Bl/6xSJL) wild-type mice. In contrast, NSPCs from APP knockout (APP-KO) mice had reduced proliferation rates compared to NSPCs from the corresponding background strain (C57Bl/6). A secreted factor, identified as cystatin C, was found to be responsible for this effect. Levels of cystatin C were higher in the Tg2576 conditioned medium and lower in the APP-KO conditioned medium. Furthermore, immunodepletion of cystatin C from the conditioned medium completely removed the ability of the conditioned medium to increase NSPC proliferation. The results demonstrate that APP expression stimulates NSPC proliferation, and that this effect is mediated via an increase in cystatin C secretion.
Funding
National Health & Medical Research Council
History
Publication title
Journal of Biological ChemistryVolume
288Issue
26Pagination
18853-18862ISSN
0021-9258Department/School
Menzies Institute for Medical ResearchPublisher
Amer Soc Biochemistry Molecular Biology IncPlace of publication
9650 Rockville Pike, Bethesda, USA, Md, 20814-3996Rights statement
Copyright 2013 The American Society for Biochemistry and Molecular Biology, Inc.Repository Status
- Restricted