دورية أكاديمية
In Vitro and In Vivo Evidence towards Fibronectin's Protective Effects against Prion Infection.
العنوان: | In Vitro and In Vivo Evidence towards Fibronectin's Protective Effects against Prion Infection. |
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المؤلفون: | Garza MC; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada., Kang SG; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada., Kim C; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada., Monleón E; Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Departamento de Anatomía e Histología Humana, Universidad de Zaragoza, IA2, IIS Aragón, 50013 Zaragoza, Spain., van der Merwe J; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada., Kramer DA; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 1C9, Canada., Fahlman R; Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada., Sim VL; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Department of Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada., Aiken J; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada.; Department of Agriculture, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 1C9, Canada., McKenzie D; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada., Cortez LM; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Department of Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada., Wille H; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada.; Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2023 Dec 15; Vol. 24 (24). Date of Electronic Publication: 2023 Dec 15. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Fibronectins*/therapeutic use , Prion Diseases*/drug therapy , Prion Diseases*/prevention & control , Prions*/metabolism , Scrapie*/metabolism, Animals ; Humans ; Cell Line ; Sheep |
مستخلص: | A distinctive signature of the prion diseases is the accumulation of the pathogenic isoform of the prion protein, PrP Sc , in the central nervous system of prion-affected humans and animals. PrP Sc is also found in peripheral tissues, raising concerns about the potential transmission of pathogenic prions through human food supplies and posing a significant risk to public health. Although muscle tissues are considered to contain levels of low prion infectivity, it has been shown that myotubes in culture efficiently propagate PrP Sc . Given the high consumption of muscle tissue, it is important to understand what factors could influence the establishment of a prion infection in muscle tissue. Here we used in vitro myotube cultures, differentiated from the C2C12 myoblast cell line (dC2C12), to identify factors affecting prion replication. A range of experimental conditions revealed that PrP Sc is tightly associated with proteins found in the systemic extracellular matrix, mostly fibronectin (FN). The interaction of PrP Sc with FN decreased prion infectivity, as determined by standard scrapie cell assay. Interestingly, the prion-resistant reserve cells in dC2C12 cultures displayed a FN-rich extracellular matrix while the prion-susceptible myotubes expressed FN at a low level. In agreement with the in vitro results, immunohistopathological analyses of tissues from sheep infected with natural scrapie demonstrated a prion susceptibility phenotype linked to an extracellular matrix with undetectable levels of FN. Conversely, PrP Sc deposits were not observed in tissues expressing FN. These data indicate that extracellular FN may act as a natural barrier against prion replication and that the extracellular matrix composition may be a crucial feature determining prion tropism in different tissues. |
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معلومات مُعتمدة: | 201300005 Alberta Prion Research Institute |
فهرسة مساهمة: | Keywords: extracellular matrix (ECM); k fibronectin; muscle; myotube; prion; reserve cells; scrapie; tropism |
المشرفين على المادة: | 0 (Fibronectins) 0 (Prions) |
تواريخ الأحداث: | Date Created: 20231223 Date Completed: 20240111 Latest Revision: 20240111 |
رمز التحديث: | 20240111 |
مُعرف محوري في PubMed: | PMC10743696 |
DOI: | 10.3390/ijms242417525 |
PMID: | 38139358 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms242417525 |