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    Wyświetlanie 1-3 z 3
    Tytuł:
    Molecular basis of mechanisms of steroid resistance in children with nephrotic syndrome
    Autorzy:
    Świerczewska, Monika
    Ostalska-Nowicka, Danuta
    Kempisty, Bartosz
    Nowicki, Michał
    Zabel, Maciej
    Powiązania:
    https://bibliotekanauki.pl/articles/1039528.pdf
    Data publikacji:
    2013
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    nephrotic syndrome
    glucocorticoid receptor
    steroid resistance
    polymorphisms
    Opis:
    Steroid therapy, due to a wide range of anti-inflammatory properties of steroids, is a basic field of treatment in many human diseases including the nephrotic syndrome in children. However, not all patients respond positively to therapy which divides them into steroid sensitive (SS) and steroid resistance (SR) individuals. Many potential factors associated with steroid resistance have been identified so far. It seems that genetic factors associated with glucocorticoid receptor α (GRα), the structure of heterocomplex of GR as well as glycoprotein P or cytochrome P450 may play a role in the induction of glucocorticoid resistance. Here we described several of the molecular mechanisms, which can regulate glucocorticoid sensitivity and resistance. Moreover, we presented genetic defects, which can lead to various effects of treatment and, in a longer perspective, enable clinicians to individualize therapies.
    Źródło:
    Acta Biochimica Polonica; 2013, 60, 3; 339-344
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    SOCS3 is epigenetically up-regulated in steroid resistant nephrotic children
    Autorzy:
    Zaorska, Katarzyna
    Zawierucha, Piotr
    Ostalska-Nowicka, Danuta
    Nowicki, Michał
    Powiązania:
    https://bibliotekanauki.pl/articles/1038853.pdf
    Data publikacji:
    2016
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    methylation
    nephrotic syndrome
    single nucleotide polymorphism
    steroid resistance
    Opis:
    Background. The mechanism of steroid resistance in children with the nephrotic syndrome is yet unknown. About 20% of patients demonstrate steroid unresponsiveness and progress to end stage renal disease. Aberrant SOCS3 and SOCS5 expression in steroid resistant and sensitive patients has previously been demonstrated. Here, we investigate genetic and epigenetic mechanisms of regulation of SOCS3 and SOCS5 transcription in nephrotic children. Methods. 76 patients with the nephrotic syndrome (40 steroid resistant and 36 steroid sensitive) and 33 matched controls were included in this study. We performed genotyping of a total of 34 single nucleotide polymorphisms for SOCS3 and SOCS5 promoters and evaluated their methylation status using MS-PCR and QMSP methods. Results. Steroid resistant patients had a significantly lower methylation of one region of SOCS3 promoter in comparison with steroid sensitive patients and controls (p < 0.0001). However, the relative methylation level in the steroid sensitive patients and controls differed significantly even before the first steroid dose (p = 0.001758). Other SOCS3 and SOCS5 promoter regions displayed no differences in methylation or were fully methylated/unmethylated in all study groups, showing site-specific methylation. The allele and genotype distribution for SOCS3 and SOCS5 markers did not differ statistically between the groups. Conclusions. We demonstrate an epigenetic mechanism of SOCS3 up-regulation in steroid resistant children with the nephrotic syndrome. The assessment of methylation/unmethylation of SOCS3 promoter might be an early marker for steroid responsiveness in NS patients.
    Źródło:
    Acta Biochimica Polonica; 2016, 63, 1; 131-138
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Polymorphic variants of MIF gene and prognosis in steroid therapy in children with idiopathic nephrotic syndrome
    Autorzy:
    Świerczewska, Monika
    Ostalska-Nowicka, Danuta
    Kempisty, Bartosz
    Szczepankiewicz, Aleksandra
    Nowicki, Michał
    Powiązania:
    https://bibliotekanauki.pl/articles/1039333.pdf
    Data publikacji:
    2014
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    nephrotic syndrome
    steroid resistance
    MIF gene
    single nucleotide polymorphism
    short tandem repeat
    Opis:
    Nephrotic syndrome (NS) is the most common reason of proteinuria in children and can be caused by the pathology of renal glomeruli. Steroid therapy is typically used in this disorder. It has been shown that MIF is a cytokine which counteracts the immunosuppressive properties of glucocorticoids. The aim of this study was looking for a correlation between MIF polymorphisms and genetic susceptibility to steroid resistance in children with INS (Idiopathic NS). Methods: The study was performed in 71 patients with INS including SRNS (steroid resistance nephrotic syndrome) (41) and SSNS (steroid sensitive nephrotic syndrome) (30) and in 30 control subjects. We employed Sanger sequencing and capillary electrophoresis. Linkage disequilibrium was made using Haploview and PHASE. Results: We didn't observe a statistical significance between SNPs detected in patients with INS and controls. Our studies revealed statistical significance for two polymorphisms: rs2070767C > T and rs2000466T > G between patients with SRNS and SSNS. The results for rs34383331T > A are close to being statistically significant. Statistical significance was revealed for CATT5/CATT6 genotype in SRNS group vs SSNS group (OR=4.604, 95%CI=1.356-15.632, p=0.0168). We found that the frequency of 5/X-CATT genotype compared with X/X-CATT genotype was significantly higher in SRNS patients vs SSNS (OR=3.167, 95%CI=1.046-9.585, p=0.0426). In linkage disequilibrium analysis we didn't show involvement in susceptibility to INS and steroid sensitive phenotype. Conclusions: Our results suggest that the role of MIF polymorphisms in the susceptibility to positive response to steroid therapy is still unresolved. It indicates that MIF may be involved in indirect and complex molecular mechanisms of steroid activity in hormone-dependent metabolic pathways in children with INS. Because of ambiguous findings, pleiotropic features of this cytokine require that more research should be undertaken.
    Źródło:
    Acta Biochimica Polonica; 2014, 61, 1; 67-75
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-3 z 3

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