Loss of hepatic miR-194 promotes liver regeneration and protects from acetaminophen-induced acute liver injury

Chang, Yi-Ming; Chen, Po-Chun; Hsu, Chien-Peng; Ma, Peng-Fang; Chen, Huey‐Ling; Hsu, Shu-Hao

doi:10.1016/j.bcp.2021.114862

Cited by 9 publications

(1 citation statement)

References 30 publications

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“…Notably, miR-122 can exert a protective function in APAP-induced hepatotoxicity by modulating CYP1A2 and CYP2E1 [12]. Additionally, depletion of miR-194 or miR-21 can promote liver regeneration and reduces APAP-induced hepatotoxic injury [13,14]. Considering these studies, regulating endogenous miRNAs in the context of ALI is suggested as a crucial therapeutic approach to alleviate liver injury.…”

Section: Introductionmentioning

confidence: 99%

Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice

Yang,

Jeong,

Kim

et al. 2024

Preprint

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Background: Cigarette smoke (CS) is a cause of premature death and exacerbates the severity of diseases not only in lungs, but also in systemic organs having no direct contact with smoke. In addition, smoking during pregnancy can have severe health consequences for both the mother and the fetus. Therefore, our aim was to evaluate effects of prenatal exposure to CS on acetaminophen (APAP)-induced acute liver injury (ALI) in offspring. Methods: Female C57BL/6 mice on day 6 of gestation were exposed to mainstream CS (MSCS) for 2 hours a day, 5 days a week for 2 weeks using a nose-only exposure system. At four weeks old, male offspring mice were injected intraperitoneally with a single dose of APAP at 300 mg/kg body weight to induce ALI. Results: Maternal MSCS exposure significantly amplified pathological effects associated with ALI as evidenced by elevated serum alanine aminotransferase levels, increased hepatocellular apoptosis, higher oxidative stress, and increased inflammation. Interestingly, maternal MSCS exposure reduced microRNA (miR)-34a-5p expression in livers of offspring. Moreover, treatment with a miR-34a-5p mimic significantly mitigated the severity of APAP-induced hepatotoxicity. Overexpression of miR-34a-5p completely abrogated adverse effects of maternal MSCS exposure in offspring with ALI. Mechanistically, miR-34a-5p significantly decreased expression levels of hepatocyte nuclear factor 4 alpha, leading to down-regulated expression of cytochrome P450 (CYP)1A2 and CYP3A11. Conclusions: Prenatal exposure to MSCS can alter the expression of miRNAs, even in the absence of additional MSCS exposure, potentially increasing susceptibility to APAP exposure in male offspring mice.

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Section: Introductionmentioning

confidence: 99%

Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice

Yang,

Jeong,

Kim

et al. 2024

Preprint

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Liver-derived extracellular vesicles from patients with hepatitis B virus-related acute-on-chronic liver failure impair hepatic regeneration by inhibiting on FGFR2 signaling via miR-218-5p

Zhang

Rao

et al. 2023

Hepatol Int

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Background: Impaired liver regeneration in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients is closely related to prognosis, whereas the mechanisms are not yet de ned. Liver-derived extracellular vesicles (EVs) may be involved in dysregulation of liver regeneration. Clarifying the underlying mechanisms will contribute to the development of improved treatments for HBV-ACLF.Methods: EVs were isolated by ultracentrifuge from liver tissues of HBV-ACLF patients (ACLF_EVs) after liver transplantation and their Function was investigated utilizing acute liver injury (ALI) mice and AML12 cells. Differentially expressed miRNAs (DE-miRNAs) were screened by deep miRNA sequencing. LNP system was applied as a carrier for targeted delivery of miRNA inhibitors to improve their effect on liver regeneration.Results: ACLF_EVs had the capacity to inhibit hepatocyte proliferation and liver regeneration, in which miRNA, especially miR-218-5p, played an important role. Mechanistically, ACLF_EVs fused directly with target hepatocytes and transferred miR-218-5p into hepatocytes, acting by suppressing FGFR2 mRNA and inhibiting the activation of ERK1/2 signaling pathways. Reducing the level of miR-218-5p expression in the liver of ACLF mice could partially restored liver regeneration ability. Conclusion: Our data reveals the mechanism underlying impaired liver regeneration in HBV-ACLF and has signi cance for the discovery of new therapeutic approaches.

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miR-194 Up-Regulates Cholesterol 7 Alpha-Hydroxylase Expression via β-Catenin Signaling and Aggravates Cholestatic Liver Diseases

Chen

Hsu

Wang

et al. 2023

The American Journal of Pathology

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Loss of hepatic miR-194 promotes liver regeneration and protects from acetaminophen-induced acute liver injury

Cited by 9 publications

References 30 publications

Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice

Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice

Liver-derived extracellular vesicles from patients with hepatitis B virus-related acute-on-chronic liver failure impair hepatic regeneration by inhibiting on FGFR2 signaling via miR-218-5p

miR-194 Up-Regulates Cholesterol 7 Alpha-Hydroxylase Expression via β-Catenin Signaling and Aggravates Cholestatic Liver Diseases

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