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Silencing of long noncoding RNA AK139328 attenuates ischemia/reperfusion injury in mouse livers.

Chen Z, Jia S, Li D, Cai J, Tu J, Geng B, Guan Y, Cui Q, Yang J - PLoS ONE (2013)

Bottom Line: Eleven of the most significantly deregulated LncRNAs were further validated by quantitative PCR assays.Furthermore, knockdown of AK139328 also reduced macrophage infitration and inhibited NF-κB activity and inflammatory cytokines expression.In conclusion, these findings revealed that deregulated LncRNAs are involved in liver ischemia/reperfusion injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing, China ; MOE Key Laboratory of Molecular Cardiovascular Science, Peking University, Beijing, China.

ABSTRACT
Recently, increasing evidences had suggested that long noncoding RNAs (LncRNAs) are involved in a wide range of physiological and pathophysiological processes. Here we determined the LncRNA expression profile using microarray technology in mouse livers after ischemia/reperfusion treatment. Seventy one LncRNAs were upregulated, and 27 LncRNAs were downregulated in ischemia/reperfusion-treated mouse livers. Eleven of the most significantly deregulated LncRNAs were further validated by quantitative PCR assays. Among the upregulated LncRNAs confirmed by quantitative PCR assays, AK139328 exhibited the highest expression level in normal mouse livers. siRNA-mediated knockdown of hepatic AK139328 decreased plasma aminotransferase activities, and reduced necrosis area in the livers with a decrease in caspase-3 activation after ischemia/reperfusion treatment. In ischemia/reperfusion liver, knockdown of AK139328 increased survival signaling proteins including phosphorylated Akt (pAkt), glycogen synthase kinase 3 (pGSK3) and endothelial nitric oxide synthase (peNOS). Furthermore, knockdown of AK139328 also reduced macrophage infitration and inhibited NF-κB activity and inflammatory cytokines expression. In conclusion, these findings revealed that deregulated LncRNAs are involved in liver ischemia/reperfusion injury. Silencing of AK139328 ameliorated ischemia/reperfusion injury in the liver with the activation of Akt signaling pathway and inhibition of NF-κB activity. LncRNA AK139328 might be a novel target for diagnosis and treatment of liver surgery or transplantation.

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Silencing of AK139328 on LncRNA expression in the livers.3 days post tail vein injection of siRNA against AK139328, the mice were subjected to ischemia/reperfusion treatment. The expression levels of deregulated LncRNAs shown Figure 3C/D were analyzed by real time PCR assays. N=10, *P<0.05 versus I/R-Scramble group. I/R-Scramble, scrambled siRNA treated mice; I/R-siAK139, siAK139328 treated mice.
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pone-0080817-g006: Silencing of AK139328 on LncRNA expression in the livers.3 days post tail vein injection of siRNA against AK139328, the mice were subjected to ischemia/reperfusion treatment. The expression levels of deregulated LncRNAs shown Figure 3C/D were analyzed by real time PCR assays. N=10, *P<0.05 versus I/R-Scramble group. I/R-Scramble, scrambled siRNA treated mice; I/R-siAK139, siAK139328 treated mice.

Mentions: H.E. staining assay revealed that silencing of AK139328 significantly attenuated liver injury after ischemia/reperfusion. In siAK139328-treated livers, necrosis area was much smaller than that in control livers (Figure 5A). Immunohistochemical staining assay revealed that silencing of siAK139328 reduced the expression level of F4/80, the biomarker of liver macrophage in the livers, suggesting the inhibition of macrophage activation (Figure 5B). Among upregulated LncRNAs, the expression level of AK054386 decreased, whereas AK087277, AK028007 and AK029601 remained unchanged after hepatic silencing of AK139328. Among downregulated LncRNAs, the expression level of AK143294 was decreased, whereas AK143693, NR-028310, ENSMUST00000151138, NR-015462 and NR-036616 remained unchanged after hepatic silencing of AK139328 (Figure 6). Overall, all these pathophysiological changes suggested that silencing of LncRNA AK139328 ameliorated ischemia/reperfusion injury in mouse livers.


Silencing of long noncoding RNA AK139328 attenuates ischemia/reperfusion injury in mouse livers.

Chen Z, Jia S, Li D, Cai J, Tu J, Geng B, Guan Y, Cui Q, Yang J - PLoS ONE (2013)

Silencing of AK139328 on LncRNA expression in the livers.3 days post tail vein injection of siRNA against AK139328, the mice were subjected to ischemia/reperfusion treatment. The expression levels of deregulated LncRNAs shown Figure 3C/D were analyzed by real time PCR assays. N=10, *P<0.05 versus I/R-Scramble group. I/R-Scramble, scrambled siRNA treated mice; I/R-siAK139, siAK139328 treated mice.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3842297&req=5

pone-0080817-g006: Silencing of AK139328 on LncRNA expression in the livers.3 days post tail vein injection of siRNA against AK139328, the mice were subjected to ischemia/reperfusion treatment. The expression levels of deregulated LncRNAs shown Figure 3C/D were analyzed by real time PCR assays. N=10, *P<0.05 versus I/R-Scramble group. I/R-Scramble, scrambled siRNA treated mice; I/R-siAK139, siAK139328 treated mice.
Mentions: H.E. staining assay revealed that silencing of AK139328 significantly attenuated liver injury after ischemia/reperfusion. In siAK139328-treated livers, necrosis area was much smaller than that in control livers (Figure 5A). Immunohistochemical staining assay revealed that silencing of siAK139328 reduced the expression level of F4/80, the biomarker of liver macrophage in the livers, suggesting the inhibition of macrophage activation (Figure 5B). Among upregulated LncRNAs, the expression level of AK054386 decreased, whereas AK087277, AK028007 and AK029601 remained unchanged after hepatic silencing of AK139328. Among downregulated LncRNAs, the expression level of AK143294 was decreased, whereas AK143693, NR-028310, ENSMUST00000151138, NR-015462 and NR-036616 remained unchanged after hepatic silencing of AK139328 (Figure 6). Overall, all these pathophysiological changes suggested that silencing of LncRNA AK139328 ameliorated ischemia/reperfusion injury in mouse livers.

Bottom Line: Eleven of the most significantly deregulated LncRNAs were further validated by quantitative PCR assays.Furthermore, knockdown of AK139328 also reduced macrophage infitration and inhibited NF-κB activity and inflammatory cytokines expression.In conclusion, these findings revealed that deregulated LncRNAs are involved in liver ischemia/reperfusion injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing, China ; MOE Key Laboratory of Molecular Cardiovascular Science, Peking University, Beijing, China.

ABSTRACT
Recently, increasing evidences had suggested that long noncoding RNAs (LncRNAs) are involved in a wide range of physiological and pathophysiological processes. Here we determined the LncRNA expression profile using microarray technology in mouse livers after ischemia/reperfusion treatment. Seventy one LncRNAs were upregulated, and 27 LncRNAs were downregulated in ischemia/reperfusion-treated mouse livers. Eleven of the most significantly deregulated LncRNAs were further validated by quantitative PCR assays. Among the upregulated LncRNAs confirmed by quantitative PCR assays, AK139328 exhibited the highest expression level in normal mouse livers. siRNA-mediated knockdown of hepatic AK139328 decreased plasma aminotransferase activities, and reduced necrosis area in the livers with a decrease in caspase-3 activation after ischemia/reperfusion treatment. In ischemia/reperfusion liver, knockdown of AK139328 increased survival signaling proteins including phosphorylated Akt (pAkt), glycogen synthase kinase 3 (pGSK3) and endothelial nitric oxide synthase (peNOS). Furthermore, knockdown of AK139328 also reduced macrophage infitration and inhibited NF-κB activity and inflammatory cytokines expression. In conclusion, these findings revealed that deregulated LncRNAs are involved in liver ischemia/reperfusion injury. Silencing of AK139328 ameliorated ischemia/reperfusion injury in the liver with the activation of Akt signaling pathway and inhibition of NF-κB activity. LncRNA AK139328 might be a novel target for diagnosis and treatment of liver surgery or transplantation.

Show MeSH
Related in: MedlinePlus