MiR-122-5p knockdown protects against APAP-mediated liver injury through up-regulating NDRG3

Yang, Zhi; Wu, Wentao; Ou, Pengcheng; Wu, Minna; Zeng, Furong; Zhou, Boping; Wu, Sihan

doi:10.1007/s11010-020-03988-0

Cited by 14 publications

(14 citation statements)

References 38 publications

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“…The result of the ACAP treatment showed significantly higher levels of miR-122 (1.32 ± 0.2 pM for mouse 1 and 1.35 ± 0.2 pM for mouse 2) as compared to that of the blank (0.8 ± 0.1 pM). One possible reason for the higher levels of miR-122 is its involvement in hepatic cell apoptosis. , It has also been reported that miR-122 knockdown also mediated ACAP-provoked hepatic cell apoptosis, which was regulated by overexpression of NDRG3 genes . As a result, the apoptosis-related proteins Bcl-w and Bcl-2 promoted the levels of miR-122 overexpression.…”

Section: Resultsmentioning

confidence: 98%

Highly Sensitive Detection of Elevated Exosomal miR-122 Levels in Radiation Injury and Hepatic Inflammation Using an Aptamer-Functionalized SERS-Sandwich Assay

Muhammad

Shao

Liu

et al. 2021

ACS Appl. Bio Mater.

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Radiation-induced organ injury is one of the major fallouts noticed during radiotherapy treatment of malignancies and other detrimental radiation exposures. MicroRNA (miRNA), which is involved in multiple critical cellular processes, is released from the cells of damaged organs in cellular vesicles, commonly known as exosomes. Specifically, exosomal miR-122 is reported to be actively involved in radiation-actuated rectal and hepatic injuries or inflammation. In this work, we developed a surface-enhanced Raman spectroscopy (SERS) assay for the quantitative and targeted detection of exosomal miR-122 in mice after drug/radiation treatments. In particular, an aptamer-functionalized magnetic capturing element and Au shell nanoparticle (NP)-based SERS tags were utilized, which upon recognition of the target miRNA constituted a “sandwich” formation, with which an 8 fM limit of detection (LOD) could be achieved. Using this SERS assay, we further found that radiation injury led to the elevated expression of exosomal miR-122 in mice at 4 h postirradiation, confirmed by the quantitative real-time PCR method. It was demonstrated that the drug-induced hepatic inflammation could also be assessed via detecting miR-122 using this SERS method. As such, this work has demonstrated the achievement of a highly selective and sensitive probe of exosomal miRNA, which may thus open a gateway for promising usage in drug/radiation-induced inflammation.

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Section: Resultsmentioning

confidence: 98%

Highly Sensitive Detection of Elevated Exosomal miR-122 Levels in Radiation Injury and Hepatic Inflammation Using an Aptamer-Functionalized SERS-Sandwich Assay

Muhammad

Shao

Liu

et al. 2021

ACS Appl. Bio Mater.

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“…Several studies have demonstrated that miR-122-5p participates in the development of various diseases ( 19 , 20 , 33 ). Ma et al ( 33 ) revealed that miR-122-5p inhibited osteosarcoma cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…Ding et al ( 19 ) demonstrated that miR-122-5p promoted skeletal muscle myogenesis via transforming growth factor β receptor 2. Yang et al ( 20 ) demonstrated that miR-122-5p downregulation can protect against acetaminophen-mediated liver damage by upregulating NDRG family member 3 expression. The results of the present study indicated that the target gene downstream of miR-122-5p was IL1RN, and that there was a direct interaction between IL1RN mRNA and miR-122-5p.…”

Section: Discussionmentioning

confidence: 99%

“…miRNAs do not encode proteins, but instead inhibit target gene expression (15)(16)(17). miR-122-5p is located at chr18q21.31, and it has been demonstrated to participate in the development of several diseases, including cancer (18), skeletal muscle myogenesis (19), drug-induced liver injury (20) and radiation-induced rectal injury (21). In addition, Lu et al (22) revealed that miR-122-5p was involved in ALI development; miR-122-5p expression in ALI was notably upregulated, and it was demonstrated to regulate pulmonary microvascular endothelial cells by affecting the dual specificity phosphatase 4 (DUSP4)/ERK signaling pathway to aggravate ALI (22).…”

Section: Introductionmentioning

confidence: 99%

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miR‑122‑5p downregulation attenuates lipopolysaccharide‑induced acute lung injury by targeting IL1RN

Zeng

Wang

2021

Exp Ther Med

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MicroRNAs (miRs) and inflammatory cytokines can induce acute lung injury (ALI), which can develop into acute respiratory distress syndrome in severe cases. Previous research has revealed that miR-122-5p participates in the development of ALI, and that its expression is positively associated with ALI. However, the mechanism by which miR-122-5p contributes to ALI remains to be determined. In the current study, TargetScan and dual luciferase reporter gene assays were used to confirm that IL-1 receptor antagonist (IL1RN) was a target of miR-122-5p. Subsequently, by referring to previous literature, a lipopolysaccharide (LPS)-induced ALI cell model was established. A549 cells were transfected with mimic control or miR-122-5p mimics for 24 h, and 10 µg LPS was used to treat the transfected cells for 12 h. The results revealed that miR-122-5p mimics decreased cell viability and promoted apoptosis. Lactate dehydrogenase (LDH) release assays indicated that miR-122-5p mimics increased LDH release. ELISA demonstrated that miR-122-5p mimics promoted TNF-α, IL-1β and IL-6 expression levels. A549 cells were transfected with inhibitor control, miR-122-5p inhibitor, miR-122-5p inhibitor + control-small interfering (si)RNA or miR-122-5p inhibitor + IL1RN-siRNA for 24 h, after which the cells were treated with 10 µg LPS for 12 h. The results revealed that the effects of the miR-122-5p inhibitor were the opposite of those of the miR-122-5p mimic. All the effects of miR-122-5p inhibitor on LPS-treated A549 cells were significantly reversed by IL1RN-siRNA. Overall, the results highlighted miR-122-5p as a potential novel target for the treatment of ALI.

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“…Liver tissues fixed in 4% neutral-buffered formalin were embedded in paraffin, cut into 5 μm-thick sections, and stained with hematoxylin and eosin (H/E) according to a standard protocol [ 46 ]. H/E-stained sections were examined using a LEICA DMI3000 B inverted microscope (Leica Biosystems, Wetzlar, Germany) and used for necrosis scoring.…”

Section: Methodsmentioning

confidence: 99%

Hepatocyte-Specific Deficiency of BAP31 Amplified Acetaminophen-Induced Hepatotoxicity via Attenuating Nrf2 Signaling Activation in Mice

Zhao¹,

Lv²,

Hu³

et al. 2021

IJMS

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Liver-specific deficiency of B-cell receptor-associated protein 31 knockout mice (BAP31-LKO) and the littermates were injected with acetaminophen (APAP), markers of liver injury, and the potential molecular mechanisms were determined. In response to APAP overdose, serum aspartate aminotransferase and alanine aminotransferase levels were increased in BAP31-LKO mice than in wild-type controls, accompanied by enhanced liver necrosis. APAP-induced apoptosis and mortality were increased. Hepatic glutathione was decreased (1.60 ± 0.31 μmol/g tissue in WT mice vs. 0.85 ± 0.14 μmol/g tissue in BAP31-LKO mice at 6 h, p < 0.05), along with reduced glutathione reductase activity and superoxide dismutase; while malondialdehyde was significantly induced (0.41 ± 0.03 nmol/mg tissue in WT mice vs. 0.50 ± 0.05 nmol/mg tissue in BAP31-LKO mice for 6 h, p < 0.05). JNK signaling activation and APAP-induced hepatic inflammation were increased in BAP31-LKO mice. The mechanism research revealed that BAP31-deficiency decreased Nrf2 mRNA stability (half-life of Nrf2 mRNA decreased from ~1.3 h to ~40 min) and miR-223 expression, led to reduced nuclear factor erythroid 2-related factor 2 (Nrf2) signaling activation and antioxidant genes induction. BAP31-deficiency decreased mitochondrial membrane potentials, reduced mitochondria-related genes expression, and resulted in mitochondrial dysfunction in the liver. Conclusions: BAP31-deficiency reduced the antioxidant response and Nrf2 signaling activation via reducing Nrf2 mRNA stabilization, enhanced JNK signaling activation, hepatic inflammation, and apoptosis, amplified APAP-induced hepatotoxicity in mice.

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MiR-122-5p knockdown protects against APAP-mediated liver injury through up-regulating NDRG3

Cited by 14 publications

References 38 publications

Highly Sensitive Detection of Elevated Exosomal miR-122 Levels in Radiation Injury and Hepatic Inflammation Using an Aptamer-Functionalized SERS-Sandwich Assay

Highly Sensitive Detection of Elevated Exosomal miR-122 Levels in Radiation Injury and Hepatic Inflammation Using an Aptamer-Functionalized SERS-Sandwich Assay

miR‑122‑5p downregulation attenuates lipopolysaccharide‑induced acute lung injury by targeting IL1RN

Hepatocyte-Specific Deficiency of BAP31 Amplified Acetaminophen-Induced Hepatotoxicity via Attenuating Nrf2 Signaling Activation in Mice

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