Dexmedetomidine protects hepatic cells against oxygen‐glucose deprivation/reperfusion injury via lncRNA CCAT1

Zhou, Zhuang; Chen, Qingsong; Wan, Lei; Zheng, Daofeng; Li, Zhongtang; Wu, Zhongjun

doi:10.1002/cbin.10996

Cited by 8 publications

(6 citation statements)

References 34 publications

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“…In addition, it has been reported that DEX can inhibit the NF-κB pathway by regulating miR-146a-3p ( 48 ) and the TLR4 pathway via the regulation of miR-129 ( 49 ). In addition to miRNAs, lncRNAs are also involved in several diseases through DEX, such as chronic obstructive pulmonary disease ( 50 ), postoperative cognitive dysfunction ( 51 ) and oxygen-glucose deprivation/reperfusion injury ( 52 ). Thus, it may be hypothesized that miRNAs or lncRNAs could mediate the effect of DEX on TLR4/NF-κB signaling.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

et al. 2022

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Dexmedetomidine (DEX) suppresses inflammatory responses and protects against organ injury. The aim of the present study was to investigate the effect of DEX on airway hyperresponsiveness (AHR) and allergic airway inflammation, as well as its underlying mechanism of action in a murine model of ovalbumin (OVA)-induced asthma. A total of 30 female BALB/c mice were divided into 6 groups (n=5 mice/group): Control, OVA, OVA + DEX (20, 30 or 50 µg/kg) and OVA + TAK-242 [a toll-like receptor 4 (TLR4) inhibitor]. The mice were intraperitoneally injected with 20, 30 or 50 µg/kg DEX 1 h before OVA challenge. AHR to inhaled methacholine (Mch) was measured, and the mice were sacrificed 24 h after the last challenge. AHR following Mch inhalation was measured using the FlexiVent apparatus. Hematoxylin and eosin, periodic acid-Schiff and Wright-Giemsa staining was performed to evaluate inflammatory cell infiltration in the lung tissue. The levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid were analyzed using ELISA, and their mRNA expression levels in the lung tissue were examined using reverse transcription-quantitative PCR. The protein expression of TLR4, NF-κB and phosphorylated (p) NF-κB in the lung tissue was also detected using immunohistochemistry. In the murine OVA-induced asthma model, DEX decreased AHR following Mch inhalation and reduced the infiltration of inflammatory cells. IL-4, IL-5 and IL-13 levels in the bronchoalveolar lavage fluid were significantly lower following DEX treatment. Furthermore, DEX treatment inhibited the expression of TLR4, NF-κB and p-NF-κB in the lung tissue and exhibited a similar effect to TAK-242 treatment. In conclusion, DEX may attenuate AHR and allergic airway inflammation by inhibiting the TLR4/NF-κB pathway. These results suggested that DEX may represent a potential anti-inflammatory agent for the treatment and management of patients with asthma.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

et al. 2022

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“…Various studies on the roles of CCAT1 and Dex in OGD/R hepatocytes have been reported [ 17 ]. This study explored the impact of CCAT1 and Dex on the apoptosis and viability of H/R-treated H9C2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, CCAT1 exerts different effects in different types of diseases. A study on hepatocyte oxygen glucose deprivation/reperfusion (OGD/R) revealed that CCAT1 plays a protective role in OGD/R hepatocytes, and this protective effect may be achieved by synergistic Dex treatment [ 17 ]. However, the effects of CCAT1 on H/R in cardiomyocytes have rarely been reported.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine protects H9C2 rat cardiomyocytes against hypoxia/reoxygenation injury by regulating the long non-coding RNA colon cancer-associated transcript 1/microRNA-8063/Wnt/β-catenin axis

Liu

2022

Bioengineered

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Dexmedetomidine (Dex) protects the heart from ischemia/reperfusion (I/R) injury. The differential expression of long non-coding RNAs (lncRNAs) is associated with myocardial injury, but whether the lncRNA colon cancer-associated transcript 1 (CCAT1) is associated with Dex-mediated myocardial protection remains unclear. In this study, a hypoxia/reoxygenation (H/R) H9C2 model was established to simulate the in vitro characteristics of I/R. CCAT1 and microRNA (miR)-8063 expression levels in H/R H9C2 cells pretreated with Dex were determined via quantitative reverse transcription-polymerase chain reaction. The survival and apoptotic rates of H9C2 cells were determined via cell counting kit-8 and flow cytometry assays. Wnt3a, Wnt5a, and β-catenin protein levels were measured via western blotting. Luciferase and RNA immunoprecipitation assays were used to explore the binding relationship between miR-8063 and CCAT1. Dex pretreatment increased H/R H9C2 cell viability and CCAT1 expression, while decreasing the cell apoptosis and Wnt3a, Wnt5a, and β-catenin protein levels. Knockdown of CCAT1 abolished the protective effects of Dex on H/R H9C2 cells, and the downregulation of miR-8063 expression eliminated the effect of CCAT1 knockdown. These results revealed that CCAT1, a sponge for miR-8063, is involved in Dex-mediated H9C2 cell H/R injury by negatively targeting miR-8063 and inactivating the Wnt/β-catenin pathway. Dex protects H9C2 cells from H/R impairment by regulating the lncRNA CCAT1/miR-8063/Wnt/β-catenin axis.

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“…18 Over-expression of lncRNA CCAT1 can inhibit the activation of apoptosis pathway in hepatocytes after hypoxia and reoxygenation. 19 Although the potential roles of a number of lncRNAs in HIRI have been explored, non-conserve RNA processing of conserved lncRNA, manifested by their distinctive function or cellular localization in cells originated from different species has recently been raised as a concern, possibly weakening the extrapolation of findings from animal or in vitro models to humans. 20 Therefore, we systematically analyzed the function of lncRNAs associated with HIRI in the present study using human liver samples collected from donor livers at the reperfusion phase and subjected them to whole transcriptome sequencing.…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of hepatic long non‐coding ribonucleic acids during liver transplantation in humans

Tang

Zhang

Liu

et al. 2023

The Journal of Gene Medicine

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Background The potential function of long non‐coding RNAs (lncRNAs) in human hepatic ischemia–reperfusion injury (HIRI) remains to be clarified. Methods Clinical samples of transplanted liver tissues from 26 patients undergoing liver transplantation (LT) and normal liver tissues from seven patients undergoing hepatic hemangiomactomy (Con) were collected. Typical samples were subjected to whole transcriptome sequencing (RNA‐seq). Differentially expressed genes between groups were identified by DEGseq and were analyzed by enrichment analysis including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. Transcription of five lncRNAs including NONHSAG039942, NONHSAG071405, NONHSAG027516, LXLOC_058190, and LXLOC_024376 that presented significant difference in RNA‐sequencing were validated by a quantitative real‐time PCR (qRT‐PCR), for which the subcellular localization and the binding ability to known human RNA‐binding proteins (RBPs) were respectively predicted by LncLocator and catRAPID genomics v2.1. Results We identified 2917 lncRNAs and 2811 mRNAs that were differentially expressed (p < 0.05 and log2 fold change > 1 or < −1) between groups (LT vs. Con). NONHSAG039942, NONHSAG071405, LXLOC_058190, and LXLOC_024376 were validated by qRT‐PCR to be significantly increased in the LT group, and were all predicted to be localized in cytoplasm or cytosol. NONHSAG039942, NONHSAG071405, and LXLOC_058190 held an RBP interaction propensity score of 98.07%, 76.95%, and 152.99%, respectively, with heterogeneous‐nuclear ribonucleoprotein U (HNRNPU). Pathways significantly activated in transplant livers that involved HNRNPU as a core enrichment gene included hypoxia, ACE2 expression, apoptosis, spliceosome formation, etc. Conclusions NONHSAG039942, NONHSAG071405, and LXLOC_058190 were significantly increased in transplant livers after reperfusion and their role in HIRI may be associated with HNRNPU, a core protein that participates in hypoxia and chromatin accessibility.

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Dexmedetomidine protects hepatic cells against oxygen‐glucose deprivation/reperfusion injury via lncRNA CCAT1

Cited by 8 publications

References 34 publications

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

Dexmedetomidine protects H9C2 rat cardiomyocytes against hypoxia/reoxygenation injury by regulating the long non-coding RNA colon cancer-associated transcript 1/microRNA-8063/Wnt/β-catenin axis

Functional analysis of hepatic long non‐coding ribonucleic acids during liver transplantation in humans

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