Fibrotic scar after experimental autoimmune encephalomyelitis inhibits oligodendrocyte differentiation
| العنوان: | Fibrotic scar after experimental autoimmune encephalomyelitis inhibits oligodendrocyte differentiation |
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| المؤلفون: | Jae K. Lee, Roberta Brambilla, Jiajun Li, Han Gao, Stephanie L. Yahn, Irene Goo |
| المصدر: | Neurobiology of disease Neurobiology of Disease, Vol 134, Iss, Pp-(2020) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Myeloid, Encephalomyelitis, Autoimmune, Experimental, Mice, Transgenic, Biology, OPCs, Article, lcsh:RC321-571, Extracellular matrix, 03 medical and health sciences, Myelination, 0302 clinical medicine, medicine, Demyelinating disease, Animals, Myeloid Cells, Perivascular fibroblasts, Remyelination, Fibroblast, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, 0303 health sciences, EAE, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Oligodendrocyte differentiation, Cell Differentiation, MS, Fibroblasts, medicine.disease, Fibrosis, White Matter, Mice, Inbred C57BL, Oligodendroglia, 030104 developmental biology, medicine.anatomical_structure, Neurology, Spinal Cord, Cancer research, Fibrotic scar, 030217 neurology & neurosurgery |
| الوصف: | Remyelination failure is a crucial component of disease progression in the autoimmune demyelinating disease Multiple Sclerosis (MS). The regenerative capacity of oligodendrocyte progenitor cells (OPCs) to replace myelinating oligodendrocytes is likely influenced by many aspects of the lesion environment including inflammatory signaling and extracellular matrix (ECM) deposition. These features of MS lesions are typically attributed to infiltrating leukocytes and reactive astrocytes. Here we demonstrate that fibroblasts also contribute to the inhibitory environment in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Using Col1α1GFPtransgenic mice, we show that perivascular fibroblasts are activated in the spinal cord at EAE onset, and infiltrate the parenchyma by the peak of behavioral deficits where they are closely associated with areas of demyelination, myeloid cell accumulation, and ECM deposition. We further show that both fibroblast conditioned media and fibroblast ECM inhibit the differentiation of OPCs into mature oligodendrocytes. Taken together, our results indicate that the fibrotic scar is a major component of EAE pathology that leads to an inhibitory environment for remyelination, thus raising the possibility that anti-fibrotic mechanisms may serve as novel therapeutic targets for MS. |
| اللغة: | English |
| تدمد: | 1095-953X 0969-9961 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c2917ae825c4ab1c89af13c5a1d5e9a http://europepmc.org/articles/PMC7547849 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3c2917ae825c4ab1c89af13c5a1d5e9a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1095953X 09699961 |
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