Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway

Gu, Xiaoxia; Xiao-hong, XU; Liao, Huihua; Wu, Ruona; Huang, Weiming; Cheng, Lü; Lu, Yiwen; Mo, Jian

doi:10.1186/s12950-021-00287-3

Cited by 9 publications

(5 citation statements)

References 53 publications

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“…Previous studies24 demonstrated that miR194 was regulated by taurine‐upregulated gene 1 ( TUG1 ), a long noncoding RNA, which is upregulated by taurine. TUG1 induced an epigenetic regulator that enhances zeste homolog 2–associated promoter methylation and can directly bind to and act as a biological sponge to reduce miR194 expression 25.…”

Section: Resultsmentioning

confidence: 99%

Probiotic‐derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation

Jiang

Liu

et al. 2022

Hepatology

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Background and Aims: Intestinal farnesoid X receptor (FXR) plays a critical role in alcohol‐associated liver disease (ALD). We aimed to investigate whether alcohol‐induced dysbiosis increased intestinal microRNA194 (miR194) that suppressed Fxr transcription and whether Lactobacillus rhamnosus GG–derived exosome‐like nanoparticles (LDNPs) protected against ALD through regulation of intestinal miR194‐FXR signaling in mice. Approach and Results: Binge‐on‐chronic alcohol exposure mouse model was utilized. In addition to the decreased ligand‐mediated FXR activation, alcohol feeding repressed intestinal Fxr transcription and increased miR194 expression. This transcriptional suppression of Fxr by miR194 was confirmed in intestinal epithelial Caco‐2 cells and mouse enteriods. The alcohol feeding–reduced intestinal FXR activation was further demonstrated by the reduced FXR reporter activity in fecal samples and by the decreased fibroblast growth factor 15 (Fgf15) messenger RNA (mRNA) in intestine and protein levels in the serum, which caused an increased hepatic bile acid synthesis and lipogeneses. We further demonstrated that alcohol feeding increased‐miR194 expression was mediated by taurine‐upregulated gene 1 (Tug1) through gut microbiota regulation of taurine metabolism. Importantly, 3‐day oral administration of LDNPs increased bile salt hydrolase (BSH)‐harboring bacteria that decreased conjugated bile acids and increased gut taurine concentration, which upregulated Tug1, leading to a suppression of intestinal miR194 expression and recovery of FXR activation. Activated FXR upregulated FGF15 signaling and subsequently reduced hepatic bile acid synthesis and lipogenesis and attenuated ALD. These protective effects of LDNPs were eliminated in intestinal Fxr ΔIEC and Fgf15 −/− mice. We further showed that miR194 was upregulated, whereas BSH activity and taurine levels were decreased in fecal samples of patients with ALD. Conclusions: Our results demonstrated that gut microbiota–mediated miR194 regulation contributes to ALD pathogenesis and to the protective effects of LDNPs through modulating intestinal FXR signaling.

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Section: Resultsmentioning

confidence: 99%

Probiotic‐derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation

Jiang

Liu

et al. 2022

Hepatology

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“…Recently, increasing evidence has suggested the regulatory effect of DEX toward the lncRNA, such as SHNG16, 35 SNHG14, 36 TUG1, 37 and PACER 38 . Our work demonstrated that DEX could reduce the expression of MALAT1 in a dose‐dependent manner, while the in vivo models also presented the ability of DEX to reduce the expression of MALAT1 in the xenograft tumors, highlighting the important role of DEX in EC via mediating the expression of MALAT1.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down‐regulation of lncRNA MALAT1

Zhang

Cai

et al. 2022

The Kaohsiung J of Med Scie

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This study aims to evaluate the effect of dexmedetomidine (DEX)—on esophageal cancer (EC) via regulating long noncoding RNA (lncRNA) metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1). The effect of DEX on MALAT1 expression and EC cell viability was detected. EC cells were divided into Blank, DEX, scrambled/MALAT1 siRNA, and DEX + control/MALAT1 groups, followed by a series of experiments including quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), western blotting, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT), Annexin V‐FITC/PI staining, wound healing, and Transwell assays. Additionally, mice were subjected to the subcutaneous injection of Eca109 cells transfected by control/MALAT1 activation lentiviral vector to construct EC models with the DEX treatment, and then the tumor volume and the expression of Ki‐67 and active caspase‐3 were determined. DEX reduced the expression of MALAT1 in EC cells in a dose‐dependent manner. DEX inhibited the viability of EC cells, but increased the cell apoptosis, which, however, was reversed by MALAT1 overexpression. Moreover, MALAT1 overexpression abolished the inhibitory effect of DEX on the epithelial–mesenchymal transition (EMT) of EC cells, with enhanced migration and invasion. Furthermore, DEX succeeded in decreasing the tumor volume with the down‐regulation of MALAT1. In comparison with the DEX group, mice in the DEX + MALAT1 group had larger tumors, with the up‐regulation of Ki‐67 and the down‐regulation of active caspase‐3. DEX can reduce the expression of MALAT1 in EC cells, thereby inhibiting the proliferation, invasion and migration, as well as EMT, and promoting the apoptosis of EC cells.

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“…Current studies indicate that lncRNAs participate in various biological processes involved in HIRI development. A few studies revealed that some lncRNAs, including TUG1[ 132 ], NEAT1[ 133 ], MALAT1[ 134 ] and Hnf4αos[ 135 ], could modulate the processes of apoptosis and inflammatory response. Other lncRNAs, such as MEG3[ 136 ], Gm4419[ 137 ], CCAT1[ 138 ] and AK054386[ 139 ] were verified to regulate apoptosis, whereas AK139328 was only found to regulate the inflammatory response[ 130 ].…”

Section: Lncrnasmentioning

confidence: 99%

Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury

Shao,

Wang,

Xiao

et al. 2023

World J Gastroenterol

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Delayed passage of meconium or constipation during the perinatal period is traditionally regarded as a signal to initiate further work up to evaluate for serious diagnoses such as Hirschsprung’s disease (HD), meconium ileus due to Cystic Fibrosis, etc. The diagnosis of HD particularly warrants invasive testing to confirm the diagnosis, such as anorectal manometry or rectal suction biopsy. What if there was another etiology of perinatal constipation, that is far lesser known? Cow’s milk protein allergy (CMPA) is often diagnosed in infants within the first few weeks of life, however, there are studies that show that the CMPA allergen can be passed from mother to an infant in-utero, therefore allowing symptoms to show as early as day one of life. The presentation is more atypical, with perinatal constipation rather than with bloody stools, diarrhea, and vomiting. The diagnosis and management would be avoidance of cow's milk protein within the diet, with results and symptom improvement in patients immediately. Therefore, we discuss whether an alternative pathway to address perinatal constipation should be further discussed and implemented to potentially avoid invasive techniques in patients. This entails first ruling out CMPA with safe, noninvasive techniques with diet modification, and if unsuccessful, then moving forward with further diagnostic modalities.

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Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway

Cited by 9 publications

References 53 publications

Probiotic‐derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation

Probiotic‐derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation

Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down‐regulation of lncRNA MALAT1

Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury

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