scholarly journals MicroRNA-223 Downregulation Promotes HBx-Induced Podocyte Pyroptosis by Targeting the NLRP3 Inflammasome

Author(s):  
Yani YU ◽  
Hui DONG ◽  
Yue ZHANG ◽  
Jingyi SUN ◽  
Baoshuang LI ◽  
...  

Abstract Hepatitis B virus (HBV) and its related protein, HBV X (HBx), play an important role in podocyte injury in HBV-associated glomerulonephritis (HBV-GN). MiR-223 is expressed in several diseases, including HBV-associated disease, while nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a major role in pyroptosis. This study aims to determine the potential function and related mechanism of miR-223 in HBx-induced podocyte pyroptosis. We observed that the results of polymerase chain reaction indicated that miR-223 was downregulated in HBx-transfected podocytes. Transfection of miR-223 mimic eliminated the expression of NLRP3 inflammasome and its related cytokines released by NLRP3 overexpression. Moreover, the transfection of HBx and NLRP3-overexpressing plasmids increased the expression of pyroptosis-related proteins especially in the presence of miR-223 inhibitors. In conclusion, miR-223 downregulation plays an important role in HBx-induced podocyte pyroptosis by targeting the NLRP3 inflammasome, suggesting that miR-223 is a potential therapeutic target for alleviating HBV-GN inflammation.

2015 ◽  
Vol 96 (3) ◽  
pp. 414-417
Author(s):  
T N Savchuk ◽  
Z K Burkitbaev ◽  
S A Abdrakhmanova ◽  
S V Skorikova ◽  
N S Kuz’min

Aim. To evaluate the effectiveness of NAT-screening (nucleic acid amplification technologies) for infections in blood donors in Kazakhstan. Methods. Statistical data of blood donors screening examinations in the Republic of Kazakhstan in 2012-2014 were evaluated. Results. In 2014, the number of examined donors increased by 3.4% compared with 2012. The number of deferrals due to positive screening results for serological markers decreased by 10.9%, while the share of such donors decreased by 13.8% [p <0.01; odds ratio (OR) - 0.86, 95% confidence interval (CI 95%) - 0.83-0.88); χ2=136.76]. In 2014, 100% of donations were screened using NAT-testing (312,510 donors). Most of the NAT-screening in Kazakhstan is performed using closed automated systems. In 2012, 1 Blood Center conducted a polymerase chain reaction screening by open circuit polymerase chain reaction systems, in 5 blood centers polymerase chain reaction was performed with manual sample preparation. In 2014, the number of deferrals due to positive NAT-testing results has increased by 44.3%, the share of such donors - by 38.7% (p <0.01; OR=1.39, 95% CI=1.15-1.67); χ2=11.82). Seronegative NAT-positive samples were discovered according to the results of discriminant test, including human immunodeficiency virus - 2 (0.8%) samples, hepatitis B virus -182 (73.4%), hepatitis C virus - 60 (24.2%), negative result - 4 (1.6%). Conclusion. The introduction of screening NAT-testing of donated blood prevented transfusion of blood infected with: human immunodeficiency virus - 1 in 150,000 donations, hepatitis B virus - 1 in 1.650 donations, hepatitis C virus - 1 in 5,000 donations.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoyu Wan ◽  
Xinbei Tian ◽  
Jun Du ◽  
Ying Lu ◽  
Yongtao Xiao

Abstract Background The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19) in the pulmonary inflammation and fibrosis of IPF. Methods Bleomycin was used to induce pulmonary inflammation and fibrosis in mice. The mRNAs and proteins expression in lung tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. H19 knockout (H19−/−) mice were generated by CRISPR/Cas9. Results The expression of H19 mRNA was up-regulated in fibrotic lungs patients with IPF as well as in lungs tissues that obtained from bleomycin-treated mice. H19−/− mice suppressed bleomycin-mediated pulmonary inflammation and inhibited the Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGF-β/Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. Conclusions Our data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for IPF.


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