دورية أكاديمية
Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses
| العنوان: | Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses |
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| المؤلفون: | Sutter, Pearl A, Willis, Cory M, Menoret, Antoine, Nicaise, Alexandra M, Sacino, Anthony, Sikkema, Arend H, Jellison, Evan R, Win, Kyaw K, Han, David K, Church, William, Baron, Wia, Vella, Anthony T, Crocker, Stephen J |
| المصدر: | Sutter , P A , Willis , C M , Menoret , A , Nicaise , A M , Sacino , A , Sikkema , A H , Jellison , E R , Win , K K , Han , D K , Church , W , Baron , W , Vella , A T & Crocker , S J 2024 , ' Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 121 , no. 5 , .... |
| سنة النشر: | 2024 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Adult, Humans, Rats, Mice, Animals, Inbred C57BL, Tissue Inhibitor of Metalloproteinase-1/genetics, Fibronectins/genetics, Fingolimod Hydrochloride/pharmacology, Astrocytes, Proteomics, Multiple Sclerosis/drug therapy, Peptide Fragments |
| الوصف: | Astrocyte activation is associated with neuropathology and the production of tissue inhibitor of metalloproteinase-1 (TIMP1). TIMP1 is a pleiotropic extracellular protein that functions both as a protease inhibitor and as a growth factor. Astrocytes that lack expression of Timp1 do not support rat oligodendrocyte progenitor cell (rOPC) differentiation, and adult global Timp1 knockout ( Timp1 KO) mice do not efficiently remyelinate following a demyelinating injury. Here, we performed an unbiased proteomic analysis and identified a fibronectin-derived peptide called Anastellin (Ana) that was unique to the Timp1 KO astrocyte secretome. Ana was found to block rOPC differentiation in vitro and enhanced the inhibitory influence of fibronectin on rOPC differentiation. Ana is known to act upon the sphingosine-1-phosphate receptor 1, and we determined that Ana also blocked the pro-myelinating effect of FTY720 (or fingolimod) on rOPC differentiation in vitro. Administration of FTY720 to wild-type C57BL/6 mice during MOG 35-55-experimental autoimmune encephalomyelitis ameliorated clinical disability while FTY720 administered to mice lacking expression of Timp1 ( Timp1 KO) had no effect. Analysis of Timp1 and fibronectin ( FN1) transcripts from primary human astrocytes from healthy and multiple sclerosis (MS) donors revealed lower TIMP1 expression was coincident with elevated FN1 in MS astrocytes. Last, analyses of proteomic databases of MS samples identified Ana peptides to be more abundant in the cerebrospinal fluid (CSF) of human MS patients with high disease activity. A role for Ana in MS as a consequence of a lack of astrocytic TIMP-1 production could influence both the efficacy of fingolimod responses and innate remyelination potential in the MS brain. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/bfd087d9-478f-4bcf-9144-8be0286d42feTest |
| DOI: | 10.1073/pnas.2306816121 |
| الإتاحة: | https://doi.org/10.1073/pnas.2306816121Test https://hdl.handle.net/11370/bfd087d9-478f-4bcf-9144-8be0286d42feTest https://research.rug.nl/en/publications/bfd087d9-478f-4bcf-9144-8be0286d42feTest https://pure.rug.nl/ws/files/929757664/sutter-et-al-2024-astrocytic-timp-1-regulates-production-of-anastellin-an-inhibitor-of-oligodendrocyte-differentiation.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2A3313EB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1073/pnas.2306816121 |
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