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Activation of Fms-l...
Activation of Fms-like tyrosine kinase 3 signaling enhances survivin expression in a mouse model of rheumatoid arthritis.
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- Andersson, Sofia E M, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Svensson, Mattias, 1982 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Erlandsson, Malin, 1972 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Dehlin, Mats, 1968 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Andersson, Karin, 1972 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Bokarewa, Maria, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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(creator_code:org_t)
- 2012-10-17
- 2012
- Engelska.
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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https://journals.plo...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Survivin is known as an inhibitor of apoptosis and a positive regulator of cell division. We have recently identified survivin as a predictor of joint destruction in patients with rheumatoid arthritis (RA). Flt3 ligand (Flt3L) is expressed in the inflamed joints and has adjuvant properties in arthritis. Studies on 90 RA patients (median age 60.5 years [range, 24-87], disease duration 10.5 years [range, 0-35]) show a strong positive association between the levels of survivin and Flt3L in blood. Here, we present experimental evidence connecting survivin and Flt3L signaling. Treatment of BALB/c mice with Flt3L led to an increase of survivin in the bone marrow and in splenic dendritic cells. Flt3L changed the profile of survivin splice variants, increasing transcription of the short survivin40 in the bone marrow. Treatment with an Flt3 inhibitor reduced total survivin expression in bone marrow and in the dendritic cell population in spleen. Inhibition of survivin transcription in mice, by shRNA lentiviral constructs, reduced the gene expression of Flt3L. We conclude that expression of survivin is a downstream event of Flt3 signaling, which serves as an essential mechanism supporting survival of leukocytes during their differentiation, and maturation of dendritic cells, in RA.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- Adult
- Aged
- Aged
- 80 and over
- Alternative Splicing
- drug effects
- genetics
- Animals
- Arthritis
- Rheumatoid
- enzymology
- pathology
- Bone Marrow
- drug effects
- metabolism
- Disease Models
- Animal
- Down-Regulation
- drug effects
- Enzyme Activation
- drug effects
- Female
- Humans
- Inhibitor of Apoptosis Proteins
- genetics
- metabolism
- Male
- Membrane Proteins
- pharmacology
- Mice
- Mice
- Inbred BALB C
- Middle Aged
- RNA
- Small Interfering
- metabolism
- Repressor Proteins
- genetics
- metabolism
- Signal Transduction
- drug effects
- Spleen
- drug effects
- metabolism
- Up-Regulation
- drug effects
- Young Adult
- fms-Like Tyrosine Kinase 3
- antagonists & inhibitors
- metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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