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1.
Chinese Medical Journal ; (24): 1342-1348, 2018.
Article Dans Anglais | WPRIM | ID: wpr-688121

Résumé

<p><b>Background</b>Lipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4.</p><p><b>Methods</b>A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-α/γ. Candidate genes affected by LXA4 were explored by transcriptome sequencing of A549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis of A549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor (ALX) inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-α expression. Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression.</p><p><b>Results</b>The A549 cell models of ALI were constructed and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream-regulated gene-1 (NDRG1) was validated by real-time-PCR and Western blot. NDRG1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG1 expression induced by LXA4. NDRG1 siRNA suppressed viability of LPS-treated A549 cells (treatment vs. control, 0.605 ± 0.063 vs. 0.878 ± 0.083, P = 0.040) and ENaC-α expression (treatment vs. control, 0.458 ± 0.038 vs. 0.711 ± 0.035, P = 0.008). LY294002 inhibited NDRG1 (treatment vs. control, 0.459 ± 0.023 vs. 0.726 ± 0.020, P = 0.001) and ENaC-α (treatment vs. control, 0.236 ± 0.021 vs. 0.814 ± 0.025, P < 0.001) expressions and serum- and glucocorticoid-inducible kinase 1 phosphorylation (treatment vs. control, 0.442 ± 0.024 vs. 1.046 ± 0.082, P = 0.002), indicating the PI3K signaling pathway was involved in regulating NDRG1 expression induced by LXA4.</p><p><b>Conclusion</b>Our research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression.</p>


Sujets)
Humains , Cellules A549 , Lésion pulmonaire aigüe , Métabolisme , Protéines du cycle cellulaire , Métabolisme , Lignée cellulaire , Canaux sodium épithéliaux , Métabolisme , Protéines et peptides de signalisation intracellulaire , Métabolisme , Lipopolysaccharides , Pharmacologie , Lipoxines , Pharmacologie , Transduction du signal
2.
Chinese Journal of Contemporary Pediatrics ; (12): 50-52, 2011.
Article Dans Chinois | WPRIM | ID: wpr-286908

Résumé

<p><b>OBJECTIVE</b>This study examined the effect of recombinant human erythropoietin (r-HuEPO) on the serum levels of neuron-specific enolase (NSE), S-100β protein and myelin basic protein (MBP) in young rats 24 hrs after lithium-pilocarpine-induced status epilepticus (SE) in order to study the potential role of r-HuEPO in epileptic brain damage.</p><p><b>METHODS</b>Forty 19-21-day-old male Sprague-Dawley (SD) rats were randomly divided into four groups (n=10): normal control group, SE, r-HuEPO pretreated-SE and r-HuEPO. SE was induced by lithium-pilocarpine. R-HuEPO (500 IU/kg) was intraperitoneally injected in the r-HuEPO pretreated-SE and r-HuEPO groups 4 hrs before SE. Serum levels of NSE, S-100β and MBP were determined 24 hrs after the SE event.</p><p><b>RESULTS</b>Serum levels of NSE, S-100β and MBP in the SE group increased significantly compared with those in the normal control and the r-HuEPO groups (P<0.05). The r-HuEPO pretreated-SE group showed significantly decreased serum levels of NSE, S-100β and MBP compared with the SE group (P<0.05).</p><p><b>CONCLUSIONS</b>r-HuEPO may reduce the expression of NSE, S-100β and MBP and thus might provide an early protective effect against epileptic brain injury.</p>


Sujets)
Animaux , Mâle , Rats , Érythropoïétine , Pharmacologie , Utilisations thérapeutiques , Protéine basique de la myéline , Sang , Facteurs de croissance nerveuse , Sang , Enolase , Sang , Rat Sprague-Dawley , Protéines recombinantes , Sous-unité bêta de la protéine liant le calcium S100 , Protéines S100 , Sang , État de mal épileptique , Sang , Traitement médicamenteux
3.
Chinese Medical Journal ; (24): 1627-1632, 2008.
Article Dans Anglais | WPRIM | ID: wpr-293946

Résumé

<p><b>BACKGROUND</b>Infantile spasms is a severe epileptic encephalopathy, which is refractory to conventional antiepileptic drugs. Adrenocorticotropic hormone (ACTH) has been the major therapy for infantile spasms; however, ACTH therapy is ineffective for some patients. The variations in the receptor genes can contribute to antiepileptic drug resistance. This study was to elucidate the possible associations between the variations of the MC2R gene and ACTH responsiveness in patients with infantile spasms.</p><p><b>METHODS</b>We screened for variations in the promoter and coding region of the MC2R gene in 91 Chinese patients with infantile spasms and 94 controls, using PCR and a direct sequencing method. The frequencies of the genotypes, alleles and reconstructed haplotypes were analyzed in the cases and controls. The association between ACTH responsiveness and genetic variations of the MC2R gene was also assessed.</p><p><b>RESULTS</b>Four single nucleotide polymorphisms (SNPs) were identified in the MC2R promoter, one of which was a novel specimen at position-2 from the transcription start site ATT, -2T > C. Three SNPs (rs1893220, rs2186944 and -2T > C) showed a significant difference between the cases and controls (P < 0.05 for all). The frequency of the common TCCT haplotype carrying four-SNP major alleles was significantly lower in the cases (39%) than in the controls (60%) (P = 0.00003). The homozygous carriers of the TCCT haplotype had a much lower relative risk than the non-carriers (RR = 0.42, 95% CI 0.26-0.70, P = 0.0001). ACTH responsiveness was strongly associated with the TCCT haplotype (P = 0.000082). Compared with non-carriers of the TCCT haplotype, the homozygous and heterozygous carriers were more responsive to ACTH therapy (P = 0.0002; P = 0.0003, respectively).</p><p><b>CONCLUSIONS</b>Our results indicated that the TCCT haplotype in the MC2R promoter is strongly associated with the responsiveness of the ACTH therapy performed on patients with infantile spasms. The polymorphisms of the MC2R promoter might be one important factor that influences the efficacy of ACTH therapy on infantile spasms.</p>


Sujets)
Femelle , Humains , Nourrisson , Mâle , Hormone corticotrope , Utilisations thérapeutiques , Haplotypes , Polymorphisme de nucléotide simple , Récepteur de la mélanocortine de type 2 , Génétique , Spasmes infantiles , Traitement médicamenteux , Génétique
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