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Functional Analyses...
Functional Analyses of the Crohn's Disease Risk Gene LACC1
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- Assadi, Ghazaleh (författare)
- Karolinska Institutet
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- Vesterlund, Liselotte (författare)
- Karolinska Institutet
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- Bonfiglio, Ferdinando (författare)
- Karolinska Institutet
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- Mazzurana, Luca (författare)
- Karolinska Institutet
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- Cordeddu, Lina (författare)
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
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- Schepis, Danika (författare)
- Rheumatology unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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- Mjösberg, Jenny (författare)
- Karolinska Institutet
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- Ruhrmann, Sabrina (författare)
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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- Fabbri, Alessia (författare)
- Karolinska Institutet
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- Vukojevic, Vladana (författare)
- Karolinska Institutet
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- Percipalle, Piergiorgio (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,New York University Abu Dhabi, United Arab Emirates
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- Salomons, Florian A. (författare)
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Laurencikiene, Jurga (författare)
- Karolinska Institutet
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- Törkvist, Leif (författare)
- Karolinska Institutet
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- Halfvarson, Jonas, 1970- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden
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- D'Amato, Mauro (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2016-12-13
- 2016
- Engelska.
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 11:12
- Relaterad länk:
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https://doi.org/10.1...
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression.Methods: We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function.Results: FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems.Conclusion: FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- art (ämneskategori)
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Assadi, Ghazaleh
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Vesterlund, Lise ...
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Bonfiglio, Ferdi ...
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Mazzurana, Luca
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Cordeddu, Lina
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Schepis, Danika
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Mjösberg, Jenny
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Ruhrmann, Sabrin ...
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Fabbri, Alessia
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Vukojevic, Vlada ...
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Percipalle, Pier ...
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Salomons, Floria ...
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Laurencikiene, J ...
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Törkvist, Leif
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Halfvarson, Jona ...
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D'Amato, Mauro
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Örebro universitet
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Stockholms universitet
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Karolinska Institutet