Overexpression of miR‐122 promotes the hepatic differentiation and maturation of mouse ESCs through a miR‐122/FoxA1/HNF4a‐positive feedback loop

Deng, Xiaogeng; Qiu, Ronglin; Wu, Yalong; Li, Zhixi; Xie, Ping; Zhang, Jie; Zhou, Jiajia; Zeng, Lexiang; Tang, Jing; Maharjan, Anu; Deng, Jiemin

doi:10.1111/liv.12239

Cited by 84 publications

(75 citation statements)

References 46 publications

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“…miR-122 plays a central role in liver development, differentiation, homeostasis, and other functions. miR-122 expression is driven by liver-enriched transcription factors (LETFs), including hepatocyte nuclear factor (HNF) 6 and 4a [29-31]. miR-122 plays a crucial role in the regulation of cholesterol and fatty acid metabolism in the adult liver.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride Accumulation via Yin Yang 1

Chen²,

Chen³

et al. 2017

Cell Physiol Biochem

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Background/Aims: An increase in intracellular lipid droplet formation and hepatic triglyceride (TG) content usually results in nonalcoholic fatty liver disease. However, the mechanisms underlying the regulation of hepatic TG homeostasis remain unclear. Methods: Oil red O staining and TG measurement were performed to determine the lipid content. miRNA expression was evaluated by quantitative PCR. A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1) by microRNA (miR)-122. The effects of miR-122 expression on YY1 and its mechanisms involving the farnesoid X receptor and small heterodimer partner (FXR-SHP) pathway were evaluated by quantitative PCR and Western blot analyses. Results: miR-122 was downregulated in free fatty acid (FFA)-induced steatotic hepatocytes, and streptozotocin and high-fat diet (STZ-HFD) induced nonalcoholic steatohepatitis (NASH) in mice. Transfection of hepatocytes with miR-122 mimics before FFA induction inhibited lipid droplet formation and TG accumulation in vitro. These results were verified by overexpressing miR-122 in the livers of STZ-HFD-induced NASH mice. The 3’-untranslated region (3’UTR) of YY1 mRNA is predicted to contain an evolutionarily conserved miR-122 binding site. In silico searches, a luciferase reporter assay and quantitative PCR analysis confirmed that miR-122 directly bound to the YY1 3’UTR to negatively regulate YY1 mRNA in HepG2 and Huh7 cells. The (FXR-SHP) signaling axis, which is downstream of YY1, may play a key role in the mechanism of miR-122-regulated lipid homeostasis. YY1-FXR-SHP signaling, which is negatively regulated by FFA, was enhanced by miR-122 overexpression. This finding was also confirmed by overexpression of miR-122 in the livers of NASH mice. Conclusions: The present results indicate that miR-122 plays an important role in lipid (particularly TG) accumulation in the liver by reducing YY1 mRNA stability to upregulate FXR-SHP signaling.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride Accumulation via Yin Yang 1

Chen²,

Chen³

et al. 2017

Cell Physiol Biochem

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“…They first investigated miR-122 levels during maturation of mouse embryonic stem cells towards hepatocytes and found a gradual increase during the induction stages [70]. Then, they showed that overexpression of miR-122 promoted hepatic differentiation and maturation of murine embryonic stem cells.…”

Section: Hepatocytesmentioning

confidence: 98%

“…When thinking about introducing miRNA-modifications in vivo (e.g. by using viral vectors), these [68][69][70]. 2) Expansion: Hepatocyte-like cells and primary hepatocytes isolated from donor organs are expanded prior to tissue engineering applications.…”

Section: Culturementioning

confidence: 99%

“…On the one hand, approaches have been developed to expand the donor organ pool by using "marginal" (e.g., steatotic or fibrotic) organs or donation after cardiac death. Strategies to improve such non-optimal organs imply donor pretreatments and ex vivo perfusion techniques to rescue Advanced Drug Delivery Reviews 88 (2015) [67][68][69][70][71][72][73][74][75][76][77] ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on "MicroRNAs in tissue engineering and regenerative medicine". the diseased organs [3,[5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNAs in liver tissue engineering — New promises for failing organs

Raschzok

Sallmon

Pratschke

et al. 2015

Advanced Drug Delivery Reviews

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“…However, hepatic differentiation was less effective in hA-DSCs when compared to human fetal liver cells. Deng et al (2014) further mechanistically investigated the role of miR-122 in hepatic differentiation. They first investigated miR-122 levels during maturation of mouse embryonic stem cells towards hepatocytes and found a gradual increase through the induction stages.…”

Section: Introductionmentioning

confidence: 99%

Analyzing the effect of MicroRNAs on Hepatogenic differentiation of Mesenchymal stem cells

Jahangirian

Alavian

2016

Int. j. adv. appl. sci.

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This research aims at analyzing the effect of microRNAs on hepatogenic Differentiation of mesenchymal stem cells. According to the results, miR-1246, miR-1290, miR-148a, miR-30a, miR-424 and miR-542-5p were definitely overexpressed during hepatic differentiation of hMSCs. Also the results indicate that ectopic overexpression of miR-122 cannot initiate hepatic differentiation of hMSCs. In other words, hMSCs can be converted into functional hepatocytes only if all the miRs (miR-122, miR-1246, miR-1290, miR-148a, miR-30a, miR-424, and miR-542-5p) are used.

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Overexpression of miR‐122 promotes the hepatic differentiation and maturation of mouse ESCs through a miR‐122/FoxA1/HNF4a‐positive feedback loop

Abstract: Overexpression of miR-122 at an appropriate stage could promote hepatic differentiation and maturation by regulating the balance between proliferation and differentiation, as well as the balance between EMT and MET, partially through a miR-122/FoxA1/HNF4a-positive feedback loop.

Cited by 84 publications

References 46 publications

MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride Accumulation via Yin Yang 1

MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride Accumulation via Yin Yang 1

MicroRNAs in liver tissue engineering — New promises for failing organs

Analyzing the effect of MicroRNAs on Hepatogenic differentiation of Mesenchymal stem cells

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