LncRNA260-specific siRNA targeting IL28RA gene inhibit cardiomyocytes hypoxic/reoxygenation injury

Gong, Ge; Yang, Xinxing; Li, Yanyan; Geng, Hong‐yu; Yang, Zhaohui; Wang, Liansheng; Kim, Hyun Jun; Lu, Xiyi

doi:10.21037/jtd.2017.07.07

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…Our previous studies have shown that downregulation of lncRNA260 regulates IL28RA and activates the JAK-STAT and PI3K/AKT signaling pathways, and this phenomenon improves the injury of hypoxic cardiomyocytes in rats [ 15 ]. This effect is thought to be related to the reduction in IL28RAV2.…”

Section: Introductionmentioning

confidence: 99%

lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing

Yang

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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The macrophage transformation of inflammatory M1 to anti-inflammatory M2 could be promoted by activating PI3K/AKT signaling pathway. In our previous study, it was found that downregulation of lncRNA260 could ameliorate hypoxic cardiomyocyte injury by regulating IL28RA through the activation of PI3K/AKT signaling pathways. It was suggested that lncRNA260 siRNA could promote the macrophages toward M2 polarization by regulating IL28RA. In this study, lncRNA260 siRNA was used to observe its effect on the polarization of murine bone marrow-derived macrophages (BMDM) and investigate its related mechanisms. lncRNA 260 specific siRNA were designed and synthesized which were transfected into murine BMDM with liposomes. The experiment was divided into three groups: Hypoxia group, Hypoxia+lncRNA 260-specific siRNA transfection group, and Normoxia group. The CD206-APC/CD11b-FITC or CD206-FITC/CD107b (Mac-3) double positive proportions were used to compare the M2 polarization proportions in the hypoxia process by using the immunofluorescence staining method. The p-AKT, Arg 1, PI3KCG, IL28RAV1, and IL28RAV2 protein expression changes were observed by using the western blot method. Compared with the Normoxia group, the M2 proportions were significantly decreased in the Hypoxia group ( P < 0.05 ). Compared with the hypoxia group, the M2 proportions were significantly increased in the Hypoxia+lncRNA260 siRNA transfection group ( P < 0.05 ). In the Hypoxia group, the ratios of Arg 1/β-Actin, p-AKT/β-Actin, PI3KCG/β-Actin, and IL28RAV1/β-Actin were significantly lower than those in the Normoxia group ( P < 0.05 ). After transfection with lncRNA260 siRNA, the ratios of Arg1/β-Actin, p-AKT/β-Actin, PI3KCG/β-Actin, and IL28RAV1/β-Actin were significantly higher than those in the Hypoxia group ( P < 0.05 ). Compared with the Normoxia group, the IL28RAV2/β-Actin in the Hypoxia group was significantly increased ( P < 0.05 ). After transfection with lncRNA260 siRNA, the ratio of IL28RAV2/β-Actin was significantly decreased than that in the Hypoxia group ( P < 0.05 ). lncRNA260 siRNA could promote the M2 polarization of the hypoxia macrophages by reducing the IL28RAV2 alternative splicing variant, which might be related to the activation of the JAK-STAT and PI3K/AKT signaling pathways. It will provide a new strategy for the anti-inflammation, antioxidative stress therapy, and cardiac remodeling after AMI.

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Section: Introductionmentioning

confidence: 99%

lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing

Yang

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Moreover, PI3KCG is a primary downstream gene regulated by IL28RA. Knockdown of IL28RA promotes cell proliferation and inhibits apoptosis by activating PI3K/AKT signaling pathways [52]. Thus, lncRNA260, as a guiding molecule, participates in the pathological process of myocardial apoptosis associated with H/R injury by regulating the transcription of IL28RA.…”

Section: Lncrna260mentioning

confidence: 99%

Long Noncoding RNAs Involved in Cardiomyocyte Apoptosis Triggered by Different Stressors

Sun

Wang

Chao

et al. 2021

J. of Cardiovasc. Trans. Res.

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Cardiomyocytes are essential to maintain the normal cardiac function. Ischemia, hypoxia, and drug stimulation can induce pathological apoptosis of cardiomyocytes which eventually leads to heart failure, arrhythmia, and other cardiovascular diseases. Understanding the molecular mechanisms that regulate cardiomyocyte apoptosis is of great significance for the prevention and treatment of cardiovascular diseases. In recent years, more and more evidences reveal that long noncoding RNAs (lncRNAs) play important regulatory roles in myocardial cell apoptosis. They can modulate the expression of apoptosisrelated genes at post-transcriptional level by altering the translation efficacy of target mRNAs or functioning as a precursor for miRNAs or competing for miRNA-mediated inhibition. Moreover, reversing the abnormal expression of lncRNAs can attenuate and even reverse the pathological apoptosis of cardiomyocytes. Therefore, apoptosis-related lncRNAs may become a potential new field for studying cardiomyocyte apoptosis and provide new ideas for the treatment of cardiovascular diseases.

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“…It was suggested that lncRNA260 might regulate IL28RA gene through trans effect and participate in the signal transmission process in the post AMI process. Our previous studies have shown that down-regulation of lncRNA260 regulates IL28RA and activates the JAK-STAT and PI3K/AKT signaling pathways, thus improving the injury of hypoxic cardiomyocytes in rats [13] , which is thought to be related to the reduction of IL28RAV2. Therefore, we speculate that lncRNA260-speci c siRNA could reduce the expression of IL28RAV2 gene, activate JAK-STAT and PI3K/AKT signaling pathways, promote the polarization of macrophages to M2-type, inhibit in ammatory response, and thus achieve certain biological effects.…”

Section: Introductionmentioning

confidence: 96%

LncRNA260 siRNA promotes M2 macrophage polarization by reducing IL28RA alternative splicing

Yang

Gong

et al. 2022

Preprint

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Background and: Regulating the macrophages toward M2 polarization has become a therapeutic target for promoting cardiac repair after acute myocardial infarction (AMI). Macrophages can promote the transformation from inflammatory M1 type to anti-inflammatory M2 type by activating PI3K/AKT signaling pathway. In our previous study, we found that down-regulation of lncRNA260 could ameliorate hypoxic cardiomyocytes injury by regulating IL28RA through the activation of PI3K/AKT signaling pathways. It was suggested that lncRNA260 siRNA could promote the macrophages toward M2 polarization by regulating IL28RA. In this study, lncRNA260 siRNA was used to observe the polarization of mouse bone marrow macrophages and investigate its related mechanisms.Objective and methods: LncRNA 260 specific siRNA were designed and synthesized which were transfected into murine bone marrow-derived macrophages (BMDM)with liposomes. The experiment was divided into three groups: hypoxia group, hypoxia + lncRNA 260 specific siRNA transfection group, Normoxia group. The CD206-FITC/CD107b (Mac-3) or CD206-APC/CD11b-FITC double positive proportions were used to compare the M2 polarization ratio in the hypoxia process by using the immunofluorescence staining method. The p-AKT, Arginase 1, PI3KCG, IL28RAV1, IL28RAV2 proteins expression changes were observed by using the western blot method.Results: Compared with the Normoxia group, the double positive ratio of CD206-FITC/ Mac-3 and CD206-APC/CD11b-FITC were both significantly decreased in Hypoxia group (P<0.05). Compared with the hypoxia group, the double positive ratio of CD206-FITC/ Mac-3 and CD206/CD11b were both significantly increased in the Hypoxia + lncRNA260 siRNA transfection group (P<0.05). In the Hypoxia group, the ratios of Arg 1/β-Actin, p-AKT/β-Actin, PI3KCG/β-Actin, IL28RAV1/β-Actin were significantly lower than those in the Normoxia group (1.00±0.01) (P<0.05). After transfection with lncRNA260 siRNA, the ratios of Arg1/β-Actin, p-AKT/β-Actin , PI3KCG/β-Actin, IL28RAV1/β-Actin were significantly higher than those in the Hypoxia group (P<0.05) .Compared with the Normoxia group, the IL28RAV2/β-Actin in the Hypoxia group was significantly increased. After transfection with lncRNA260 siRNA, the ratio of IL28RAV2/β-Actin was significantly decreased than that in the Hypoxia group (P<0.05).Conclusion: LncRNA260 siRNA could promote the M2 polarization of the hypoxia macrophages by reducing the IL28RAV2 alternative splicing variant, which might be related to the activation of the JAK-STAT and PI3K/AKT signaling pathways.

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LncRNA260-specific siRNA targeting IL28RA gene inhibit cardiomyocytes hypoxic/reoxygenation injury

Cited by 5 publications

References 17 publications

lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing

lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing

Long Noncoding RNAs Involved in Cardiomyocyte Apoptosis Triggered by Different Stressors

LncRNA260 siRNA promotes M2 macrophage polarization by reducing IL28RA alternative splicing

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