Immune-mediated β-cell destruction in vitro and in vivo—A pivotal role for galectin-3
| Autor: | Krzysztof Wrzesinski, T. Sparre, Martin R. Larsen, Stephen J. Fey, Camillo Ricordi, Ulla Bjerre Christensen, Joachim Størling, Karin Nielsen, Zenia M Størling, Allan E. Karlsen, Peter Mose Larsen, Peter Roepstorff, Peter E. Heding, Ingrid Kockum, Holger Luthman, Jørn Nerup, Jesper Johannesen, O. P. Kristiansen, Amer Mahmood, Flemming Pociot |
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| Rok vydání: | 2006 |
| Předmět: |
Proteomics
Gene isoform Candidate gene endocrine system diseases Galectin 3 Biophysics Apoptosis Biology medicine.disease_cause Polymorphism Single Nucleotide Biochemistry Immune system In vivo Insulin-Secreting Cells medicine Animals Humans RNA Messenger Molecular Biology Gene Galectin Mutation Phosphotransferases Rats Inbred Strains Genomics Cell Biology Rats Cell biology Diabetes Mellitus Type 1 Gene Expression Regulation Haplotypes Immunology Cytokines Beta cell Interleukin-1 |
| Zdroj: | Karlsen, A E, Størling, Z M, Sparre, T, Larsen, M R, Mahmood, A, Størling, J, Roepstorff, P, Wrzesinski, K, Larsen, P M, Fey, S, Nielsen, K, Heding, P, Ricordi, C, Johannesen, J, Kristiansen, O P, Christensen, U B, Kockum, I, Luthman, H, Nerup, J & Pociot, F 2006, ' Immune-mediated beta-cell destruction in vitro and in vivo-A pivotal role for galectin-3 ', Biochemical and Biophysical Research Communications, vol. 344, no. 1, pp. 406-415 . https://doi.org/10.1016/j.bbrc.2006.03.105 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2006.03.105 |
| Popis: | Udgivelsesdato: 2006-May-26 Pro-apoptotic cytokines are toxic to the pancreatic beta-cells and have been associated with the pathogenesis of Type 1 diabetes (T1D). Proteome analysis of IL-1beta exposed isolated rat islets identified galectin-3 (gal-3) as the most up-regulated protein. Here analysis of human and rat islets and insulinoma cells confirmed IL-1beta regulated gal-3 expression of several gal-3 isoforms and a complex in vivo expression profile during diabetes development in rats. Over-expression of gal-3 protected beta-cells against IL-1beta toxicity, with a complete blockage of JNK phosphorylation, essential for IL-1-mediated apoptosis. Mutation scanning of regulatory and coding regions of the gal-3 gene (LGALS3) identified six polymorphisms. A haplotype comprising three cSNPs showed significantly increased transmission to unaffected offspring in 257 T1D families and replicated in an independent set of 170 T1D families. In summary, combined proteome-transcriptome-genome and functional analyses identify gal-3 as a candidate gene/protein in T1D susceptibility that may prove valuable in future intervention/prevention strategies. |
| Databáze: | OpenAIRE |
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