Publication: Exploring the factors underlying remyelination arrest by studying the post-transcriptional regulatory mechanisms of cystatin F gene
Issued Date
2020-01-01
Resource Type
ISSN
14714159
00223042
00223042
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2-s2.0-85091763330
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Neurochemistry. (2020)
Suggested Citation
Jiayi Li, Wilaiwan Wisessmith Durose, Junko Ito, Akiyoshi Kakita, Yohei Iguchi, Masahisa Katsuno, Kazuo Kunisawa, Takeshi Shimizu, Kazuhiro Ikenaka Exploring the factors underlying remyelination arrest by studying the post-transcriptional regulatory mechanisms of cystatin F gene. Journal of Neurochemistry. (2020). doi:10.1111/jnc.15190 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/59906
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Title
Exploring the factors underlying remyelination arrest by studying the post-transcriptional regulatory mechanisms of cystatin F gene
Other Contributor(s)
Nagoya University Graduate School of Medicine
University of Minnesota Twin Cities
Fujita Health University
Nagoya City University
Niigata University
National Institutes of Natural Sciences - National Institute for Physiological Sciences
The Graduate University for Advanced Studies
Mahidol University
University of Minnesota Twin Cities
Fujita Health University
Nagoya City University
Niigata University
National Institutes of Natural Sciences - National Institute for Physiological Sciences
The Graduate University for Advanced Studies
Mahidol University
Abstract
© 2020 International Society for Neurochemistry Remyelination plays an important role in determining the fate of demyelinating disorders. However, it is arrested during chronic disease states. Cystatin F, a papain-like lysosomal cysteine proteinase inhibitor, is a crucial regulator of demyelination and remyelination. Using hemizygous proteolipid protein transgenic 4e (PLP4e/-) mice, an animal model of chronic demyelination, we found that cystatin F mRNA expression was induced at 2.5 months of age and up-regulated in the early phase of demyelination, but significantly decreased in the chronic phase. We next investigated cystatin F regulatory factors as potential mechanisms of remyelination arrest in chronic demyelinating disorders. We used the CysF-STOP-tetO::Iba-mtTA mouse model, in which cystatin F gene expression is driven by the tetracycline operator. Interestingly, we found that forced cystatin F mRNA over-expression was eventually decreased. Our findings show that cystatin F expression is modulated post-transcriptionally. We next identified embryonic lethal, abnormal vision, drosophila like RNA-binding protein 1 (ELAVL-1), and miR29a as cystatin F mRNA stabilizing and destabilizing factors, respectively. These roles were confirmed in vitro in NIH3T3 cells. Using postmortem plaque samples from human multiple sclerosis patients, we also confirmed that ELAVL-1 expression was highly correlated with the previously reported expression pattern of cystatin F. These data indicate the important roles of ELAVL-1 and miR29a in regulating cystatin F expression. Furthermore, they provide new insights into potential therapeutic targets for demyelinating disorders. (Figure presented.).
