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

He, Shuang-Hui; Guo, Weihong; Deng, Feihong; Chen, Kequan; Jiang, Yu; Dong, Meichen; Peng, Liang; Chen, Xueqing

doi:10.1080/21691401.2018.1453830

Cited by 25 publications

(21 citation statements)

References 45 publications

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“…MicroRNAs play an important role in a variety of diseases [18][19][20] including the lipid metabolic disorder [21,22], because they can regulate a wide range of growth and development processes [7]. Recent studies indicate that miR-27a [23], miR-194 [24] and miR-146b [25] can target different genes to regulate the development of NAFLD. According to our previous research, miR-455 is the key regulator of BAT in the process of differentiation [9] and may have an effect on the regulation of lipid synthesis.…”

Section: Discussionmentioning

confidence: 99%

MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice

et al. 2020

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MiR-455 has been verified a key regulator of brown adipose tissue and adipose tissue-specific overexpression of miR-455 (ap2-miR-455) mice could combat high-fat-diet-induced obesity. This study is to verify overexpression of miR-455 could ameliorate the lipid accumulation and metabolism in the liver of db/db diabetic mice and explore the potential mechanisms. Diabetic mice (db/db) and control mice (db/ m) were randomly divided into four groups. After overexpression of miR-455 in the liver of db/db mice, the triglycerides level in both serum and liver decreased, the lipid deposit in liver was improved, the expression of fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase (ACCα) was also significantly down-regulated. TargetScan indicated that suppressor of cytokine signalling 3 (SOCS3) is predicated to target miR-455 and the protein of SOCS3 in the liver of db/db mice after intervention was significantly decreased. The dual luciferase reporter assay showed that SOCS3 was target gene of miR-455. In vitro, in Palmitate (PA)stimulated human normal liver (LO2) cells, transfected miR-455 mimic could significantly inhibit the expression of SOCS3, while transfected miR-455 inhibitor could up-regulate the expression of SOCS3. Transfecting LO2 cells with siRNA of SOCS3 could significantly down-regulate the protein expression of SREBP-1c and ACCα. Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene SOCS3.

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Section: Discussionmentioning

confidence: 99%

MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice

et al. 2020

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“…The immunostained sections were examined with an Olympus IX73 microscope (Olympus, Tokyo, Japan). Positive staining for a-SMA, Shh, PTH1R, PTHLH and GLI2 was semi-quantified according to a previously described method [32].…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…Computer-aided quantification of the fibrotic areas was performed on Sirius Red-stained liver sections from different groups (n ¼ 5 in each group), as indicated in the relevant figure legends. The fibrotic areas were calculated according to a previously described method [32].…”

Section: Sirius Red Staining and Morphometrymentioning

confidence: 99%

Parathyroid hormone-related protein activates HSCs via hedgehog signalling during liver fibrosis development

Tang

Diao

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Recently, we showed that parathyroid hormone-like hormone (PTHLH), a cytokine-like polyprotein, is critical for extracellular matrix (ECM) deposition through the activation of hepatic stellate cells (HSCs).Here, we show that N-terminal PTHLH is secreted into the supernatant of injured hepatocytes, its expression is positively correlated with liver fibrosis severity based on mice liver biopsies, and it is primarily expressed in the cytoplasm of hepatocytes along the fibrous septa of fibrotic livers. PTHLH overexpression in mice was achieved through adeno-associated virus-mediated gene delivery (AAV9-PTHLH), and liver fibrosis was induced with carbon tetrachloride (CCl 4 ). We observed that AAV9-PTHLH induced spontaneous development of liver fibrosis and increased sensitivity to CCl 4 . PTHLH increased Hedgehog (Hh) pathway activation in a PTH1R-dependent manner, and the effect of PTHLH was primarily mediated by protein kinase C (PKC) h. PTHLH-mediated PTH1R-PKC h pathway activation is a key event in the profibrotic Hh-dependent activation of HSCs.

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“…Studies on mice and nonhuman primates suggested that an miR-33 blockade results in changes in the expression of hepatic genes involved in lipid metabolism; further, it ameliorates dyslipidemia that is induced by a high-fat diet (HFD) (Rayner et al, 2011a;Rayner et al, 2011b). However, the traditional methods used in these studies yielded a limited delivery efficacy in vivo and inhibited further applications in clinic (He et al, 2018). One of the problems associated with the low efficiency of the traditional methods is that they require high doses of agents, with mice needing 10 mg/kg of anti-miR-33 oligonucleotides per week (Rayner et al, 2011b).…”

Section: Introductionmentioning

confidence: 99%

Delivery of microRNA-33 Antagomirs by Mesoporous Silica Nanoparticles to Ameliorate Lipid Metabolic Disorders

Tao

Wang

et al. 2020

Front. Pharmacol.

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Lipid metabolic disorders have become a major global public health concern. Fatty liver and dyslipidemia are major manifestations of these disorders. Recently, MicroRNA-33 (miR-33), a post-transcriptional regulator of genes involved in cholesterol efflux and fatty acid oxidation, has been considered as a good therapeutic target for these disorders. However, the traditional methods of gene therapy impede their further clinical transformation into a mature treatment system. To counter this problem, in this study we used mesoporous silica nanoparticles (MSNs) as nanocarriers to deliver miR-33 antagomirs developing nanocomposites miR-MSNs. We observed that the hepatocellular uptake of miR-33 antagomirs increased by ∼5 times when they were delivered using miR-MSNs. The regulation effects of miR-MSNs on miR-33 and several genes involved in lipid metabolism were confirmed in L02 cells. In a high-fat diet fed mice, miR-33 intervention via miR-MSNs lowered the serum triglyceride levels remarkably by 18.9% and reduced hepatic steatosis. Thus, our results provide a proof-of-concept for a potential strategy to ameliorate lipid metabolic disorders.

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

Cited by 25 publications

References 45 publications

MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice

MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice

Parathyroid hormone-related protein activates HSCs via hedgehog signalling during liver fibrosis development

Delivery of microRNA-33 Antagomirs by Mesoporous Silica Nanoparticles to Ameliorate Lipid Metabolic Disorders

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