Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster

Zeng, Xianyi; Zhang, Yanqiong; He, Xiaomin; Wan, Lin‐Yan; Wang, Hu; Ni, Yi-Ran; Wang, Jie; Wu, Jiangfeng; Liu, Changbai

doi:10.18632/oncotarget.13365

Cited by 15 publications

(17 citation statements)

References 37 publications

(48 reference statements)

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“…MiR-24 is also a member of miR-23b cluster that could be used as non-invasive biomarkers in fibrogenic liver diseases (Oksuzet al, 2015). Although some other studies on miR-23b cluster regulating HSC activation are inconsistent with our study (Yuan et al, 2011;Zeng et al, 2016;Hall et al, 2017;Rogler et al, 2017), a quite recent study showed that knockdown of miR-23, miR-27, and miR-24 had a distinctly blocking effect on mouse liver fibrosis (Rogler et al, 2017), which is consistent with our findings.…”

Section: Discussionsupporting

confidence: 90%

LncRNA Gm5091 alleviates alcoholic hepatic fibrosis by sponging miR‐27b/23b/24 in mice

Zhou

Yuan

2018

Cell Biology International

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The regulatory roles of lncRNAs in the development of alcoholic hepatic fibrosis (AHF) have not been revealed. Here, we found lncRNA Gm5091 was being downregulated in mouse hepatic stellate cells (HSCs) during AHF. Then, Gm5091 was, respectively, overexpressed and knocked down in alcohol-treated primary HSCs. Our results showed that Gm5091 negatively regulated cell migration, ROS content, IL-1β secretion, and expression of Collagen I and markers of HSC activation including α-SMA and Desmin. Furthermore, bioinformatics analysis showed that Gm5091 sequence contained binding sites of miR-27b, miR-23b, and miR-24, and we proved that miR-27b/23b/24 all bound to Gm5091 by using RNA pull-down assay. Full-length Gm5091 could decrease the miR-27b/23b/24 levels, but the truncated Gm5091 deleting the binding sites could not. Finally, we confirmed that full-length Gm5091 could alleviate AHF in vivo, but the truncated Gm5091 could not. In conclusion, lncRNA Gm5091 alleviates mouse AHF by sponging miR-27b/23b/24.

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Section: Discussionsupporting

confidence: 90%

LncRNA Gm5091 alleviates alcoholic hepatic fibrosis by sponging miR‐27b/23b/24 in mice

Zhou

Yuan

2018

Cell Biology International

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“…However, it is also an important molecule for adjusting the liver’s response to a HFD and directing its overall regulation for processing free fatty acids, as well as liver regeneration and activation of quiescent hepatic stellate cells (HSCs) [ 17 , 18 ]. In fact, PPARγ deletion in mouse hepatocytes has been shown to be protective against development of steatosis [ 19 , 20 , 21 ], but this also exacerbates insulin resistance [ 20 , 22 ]. There are many studies investigating the effects of an HFD on the overall metabolism and PPARγ regulation pathways in various metabolic tissues.…”

Section: Introductionmentioning

confidence: 99%

Effect of Chronic Western Diets on Non-Alcoholic Fatty Liver of Male Mice Modifying the PPAR-γ Pathway via miR-27b-5p Regulation

Zhang

Powell

Kay

et al. 2021

IJMS

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Western diets contribute to metabolic diseases. However, the effects of various diets and epigenetic mechanisms are mostly unknown. Here, six week-old C57BL/6J male and female mice were fed with a low-fat diet (LFD), high-fat diet (HFD), and high-fat high-fructose diet (HFD-HF) for 20 weeks. We determined that HFD-HF or HFD mice experienced significant metabolic dysregulation compared to the LFD. HFD-HF and HFD-fed male mice showed significantly increased body weight, liver size, and fasting glucose levels with downregulated PPARγ, SCD1, and FAS protein expression. In contrast, female mice were less affected by HFD and HFD-HF. As miR-27b contains a seed sequence in PPARγ, it was discovered that these changes are accompanied by male-specific upregulation of miR-27b-5p, which is even more pronounced in the HFD-HF group (p < 0.01 vs. LFD) compared to the HFD group (p < 0.05 vs. LFD). Other miR-27 subtypes were increased but not significantly. HFD-HF showed insignificant changes in fibrosis markers when compared to LFD. Interestingly, fat ballooning in hepatocytes was increased in HFD-fed mice compared to HFD-HF fed mice, however, the HFD-HF liver showed an increase in the number of small cells. Here, we concluded that chronic Western diet-composition administered for 20 weeks may surpass the non-alcoholic fatty liver (NAFL) stage but may be at an intermediate stage between fatty liver and fibrosis via miR-27b-5p-induced PPARγ downregulation.

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“… 6 , 7 , 8 Recently, miR-23b was reported to suppress activation of hepatic stellate cells by targeting gremlin1 and had a pivotal role in the process of hepatic fibrosis. 9 However, until now, the roles of miR-23b in HCC progression and the mechanism underlying the effects of miR-23b on HCC tumorigenesis are still needed to be explored.…”

mentioning

confidence: 99%

MicroRNA-23b functions as an oncogene and activates AKT/GSK3β/β-catenin signaling by targeting ST7L in hepatocellular carcinoma

Zhuang

Wang

et al. 2017

Cell Death Dis

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Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life worldwide, whereas the etiology and pathogenesis of HCC have not been fully determined. In the past few years, many microRNAs (miRNAs) have been proved to have important roles in tumorigenesis of HCC. In this study, we found that miR-23b was significantly upregulated in tumor tissues of HCC patients. Functional tests showed that miR-23b could promote HCC cell proliferation and metastasis in vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a direct target of miR-23b and involved in the promotion effects of miR-23b on HCC tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could interact with the carboxyl terminal region of AKT and suppress AKT/GSK3β/β-catenin pathway in HCC cells. In conclusion, our study revealed important roles of miR-23b and ST7L in progression of HCC.

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Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster

Cited by 15 publications

References 37 publications

LncRNA Gm5091 alleviates alcoholic hepatic fibrosis by sponging miR‐27b/23b/24 in mice

LncRNA Gm5091 alleviates alcoholic hepatic fibrosis by sponging miR‐27b/23b/24 in mice

Effect of Chronic Western Diets on Non-Alcoholic Fatty Liver of Male Mice Modifying the PPAR-γ Pathway via miR-27b-5p Regulation

MicroRNA-23b functions as an oncogene and activates AKT/GSK3β/β-catenin signaling by targeting ST7L in hepatocellular carcinoma

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