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Expression Profile of Six RNA-Binding Proteins in Pulmonary Sarcoidosis
Z. Navratilova, E. Novosadova, M. Hagemann-Jensen, S. Kullberg, V. Kolek, J. Grunewald, M. Petrek,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu srovnávací studie, časopisecké články
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Directory of Open Access Journals
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- MeSH
- bronchiální astma genetika metabolismus MeSH
- chronická obstrukční plicní nemoc genetika metabolismus MeSH
- dospělí MeSH
- fosfohydroláza PTEN genetika metabolismus MeSH
- fosfoproteiny genetika metabolismus MeSH
- GPI-vázané proteiny genetika metabolismus MeSH
- heterogenní jaderný ribonukleoprotein D genetika metabolismus MeSH
- HuR protein genetika metabolismus MeSH
- idiopatické intersticiální pneumonie genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- plicní sarkoidóza genetika metabolismus MeSH
- poly(A)-vazebné proteiny genetika metabolismus MeSH
- proteiny vázající RNA genetika metabolismus MeSH
- regulace genové exprese MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- T-lymfocyty metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: Sarcoidosis is characterised by up-regulation of cytokines and chemokine ligands/receptors and proteolytic enzymes. This pro-inflammatory profile is regulated post-transcriptionally by RNA-binding proteins (RBPs). We investigated in vivo expression of six RBPs (AUF1, HuR, NCL, TIA, TIAR, PCBP2) and two inhibitors of proteolytic enzymes (RECK, PTEN) in pulmonary sarcoidosis and compared it to the expression in four control groups of healthy individuals and patients with other respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma and idiopathic interstitial pneumonias (IIPs). METHODS: RT-PCR was used to quantify the mRNAs in bronchoalveolar (BA) cells obtained from 50 sarcoidosis patients, 23 healthy controls, 30 COPD, 19 asthmatic and 19 IIPs patients. Flow cytometry was used to assess intracellular protein expression of AUF1 and HuR in peripheral blood T lymphocytes (PBTLs) obtained from 9 sarcoidosis patients and 6 healthy controls. RESULTS: Taking the stringent conditions for multiple comparisons into consideration, we consistently observed in the primary analysis including all patients regardless of smoking status as well as in the subsequent sub-analysis limited for never smokers that the BA mRNA expression of AUF1 (p<0.001), TIA (p<0.001), NCL (p<0.01) and RECK (p<0.05) was decreased in sarcoidosis compared to healthy controls. TIA mRNA was also decreased in sarcoidosis compared to both obstructive pulmonary diseases (COPD and asthma; p<0.001) but not compared to IIPs. There were several positive correlations between RECK mRNA and RBP mRNAs in BA cells. Also sarcoidosis CD3+, CD4+ and CD8+ PBTLs displayed lower mean fluorescence intensity of AUF1 (p≤0.02) and HuR (p≤0.03) proteins than control healthy PBTLs. CONCLUSION: mRNA expressions of three RBPs (AUF1, TIA and NCL) and their potential target mRNA encoding RECK in BA cells and additionally protein expression of AUF1 and HuR in PBTLs were down-regulated in our sarcoidosis patients compared to healthy individuals. Its significance, e.g. for stability of mRNAs encoding pro-inflammatory factors, should be further explored in sarcoidosis.
Department of Respiratory Medicine Palacky University Olomouc Czech Republic
Respiratory Medicine Unit Department of Medicine Karolinska Institutet Stockholm Sweden
Citace poskytuje Crossref.org
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