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- W2141030054 abstract "Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched 'pre-myelinating' MBP+ / PLP+ oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients." @default.
- W2141030054 created "2016-06-24" @default.
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- W2141030054 date "2015-04-22" @default.
- W2141030054 modified "2023-10-14" @default.
- W2141030054 title "Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9" @default.
- W2141030054 cites W1485262693 @default.
- W2141030054 cites W1495522011 @default.
- W2141030054 cites W1499500424 @default.
- W2141030054 cites W1502312172 @default.
- W2141030054 cites W1689660630 @default.
- W2141030054 cites W1925136148 @default.
- W2141030054 cites W1953941107 @default.
- W2141030054 cites W1963550496 @default.
- W2141030054 cites W1964544761 @default.
- W2141030054 cites W1965358479 @default.
- W2141030054 cites W1968091833 @default.
- W2141030054 cites W1970757672 @default.
- W2141030054 cites W1973520165 @default.
- W2141030054 cites W1974656309 @default.
- W2141030054 cites W1979552960 @default.
- W2141030054 cites W1982222429 @default.
- W2141030054 cites W1984551835 @default.
- W2141030054 cites W1991592834 @default.
- W2141030054 cites W1994717165 @default.
- W2141030054 cites W1996131506 @default.
- W2141030054 cites W1998225973 @default.
- W2141030054 cites W1998601032 @default.
- W2141030054 cites W2000108033 @default.
- W2141030054 cites W2000698657 @default.
- W2141030054 cites W2011557383 @default.
- W2141030054 cites W2017326823 @default.
- W2141030054 cites W2021474702 @default.
- W2141030054 cites W2024751716 @default.
- W2141030054 cites W2026321358 @default.
- W2141030054 cites W2031196287 @default.
- W2141030054 cites W2031931278 @default.
- W2141030054 cites W2048082433 @default.
- W2141030054 cites W2048206988 @default.
- W2141030054 cites W2050596253 @default.
- W2141030054 cites W2053166138 @default.
- W2141030054 cites W2056999895 @default.
- W2141030054 cites W2057429800 @default.
- W2141030054 cites W2058358434 @default.
- W2141030054 cites W2061158475 @default.
- W2141030054 cites W2061293847 @default.
- W2141030054 cites W2061522969 @default.
- W2141030054 cites W2062326815 @default.
- W2141030054 cites W2062870333 @default.
- W2141030054 cites W2070640008 @default.
- W2141030054 cites W2070800078 @default.
- W2141030054 cites W2077702475 @default.
- W2141030054 cites W2077902472 @default.
- W2141030054 cites W2078482008 @default.
- W2141030054 cites W2081474240 @default.
- W2141030054 cites W2082600118 @default.
- W2141030054 cites W2083092470 @default.
- W2141030054 cites W2084194517 @default.
- W2141030054 cites W2085029391 @default.
- W2141030054 cites W2085383857 @default.
- W2141030054 cites W2086237072 @default.
- W2141030054 cites W2087398290 @default.
- W2141030054 cites W2090177945 @default.
- W2141030054 cites W2095040041 @default.
- W2141030054 cites W2096936001 @default.
- W2141030054 cites W2100119722 @default.
- W2141030054 cites W2100555346 @default.
- W2141030054 cites W2102828742 @default.
- W2141030054 cites W2103781798 @default.
- W2141030054 cites W2104447446 @default.
- W2141030054 cites W2107277218 @default.
- W2141030054 cites W2107554012 @default.
- W2141030054 cites W2108005154 @default.
- W2141030054 cites W2111428020 @default.
- W2141030054 cites W2114570899 @default.
- W2141030054 cites W2122665472 @default.
- W2141030054 cites W2123444403 @default.
- W2141030054 cites W2124364681 @default.
- W2141030054 cites W2135949891 @default.
- W2141030054 cites W2139729824 @default.
- W2141030054 cites W2147425081 @default.