Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis

Jin, Xi; Liu, Jiang; Chen, Yipeng; Xiang, Zun; Ding, Jinwang; Li, Youming

doi:10.1371/journal.pone.0174218

Cited by 12 publications

(10 citation statements)

References 36 publications

(39 reference statements)

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“…To gain insight into the expression changes of various miRNAs by YD during liver fibrosis, we screened several miRNAs associated with liver fibrosis and inflammation in mice by RT-PCR, including miR-125, miR-155, let-7a, miR-150, and miR-146 15 , 16 , 17 . As shown in Supporting Information Fig.…”

Section: Resultsmentioning

confidence: 99%

The antimicrobial peptide YD attenuates inflammation via miR-155 targeting CASP12 during liver fibrosis

Wang

Chen

et al. 2021

Acta Pharmaceutica Sinica B

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The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro . These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α -smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF- κ B signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF- κ B pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155– Casp12 –NF- κ B axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

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Section: Resultsmentioning

confidence: 99%

The antimicrobial peptide YD attenuates inflammation via miR-155 targeting CASP12 during liver fibrosis

Wang

Chen

et al. 2021

Acta Pharmaceutica Sinica B

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“…Increased expression of hepatocellular carcinoma down-regulated mitochondrial carrier protein (HDMCP) was identified in NASH animal models and HFFA-72h cultured L02 cells. The miR-146-HDMCP-downstream effector pathway is involved in NASH[ 42 ]. Collectively, previous studies have demonstrated that apoptosis resulting from mitochondrial injury is associated with the progression of NAFLD and NASH.…”

Section: Bcl-2 Family Members and Mitochondria In The Progression Of mentioning

confidence: 99%

Apoptosis and non-alcoholic fatty liver diseases

Kanda

Matsuoka

Yamazaki

et al. 2018

WJG

209

145

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The number of patients with nonalcoholic fatty liver diseases (NAFLD) including nonalcoholic steatohepatitis (NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma (HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.

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“…NASH was characterized by steatosis with inflammation. The previous study showed that upregulation of miR-146b mimic could significantly inhibit the lipid accumulation and inflammation both in vitro and in vivo [26,45]. However, despite its important roles in anti-steatosis and anti-inflammation, the potential therapeutic of miR-146b mimic has not been adequately evaluated in a translational research setting.…”

Section: Discussionmentioning

confidence: 99%

Targeted delivery of microRNA 146b mimic to hepatocytes by lactosylated PDMAEMA nanoparticles for the treatment of NAFLD

Guo

Deng

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine-choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA. We coupled miR-146b mimic with Lac-PDMAEMA and then were administrated to NAFLD mice model, which could obviously alleviate the hepatic steatosis. Lac-PDMAEMA effectively delivered miR-146b mimic to hepatocytes with a ∼8-fold upregulation of miR-146b mimic targeting MyD88 and IRAK1, and in turn suppressed the expression of PPARγ. Meanwhile, TNF-α and IL-6 mRNA levels were decreased after administration of Lac-PDMAEMA/miR-146b mimic. So, we made a conclusion that targeted delivering miR-146b mimic to the hepatocytes by, coupling Lac-PDMAEMA nanoparticles could effectively alleviate the hepatic steatosis in NAFLD mice, which maybe bring a new and effective way to intervene and therapy the NAFLD.

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Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis

Cited by 12 publications

References 36 publications

The antimicrobial peptide YD attenuates inflammation via miR-155 targeting CASP12 during liver fibrosis

The antimicrobial peptide YD attenuates inflammation via miR-155 targeting CASP12 during liver fibrosis

Apoptosis and non-alcoholic fatty liver diseases

Targeted delivery of microRNA 146b mimic to hepatocytes by lactosylated PDMAEMA nanoparticles for the treatment of NAFLD

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