Inhibition of micro<scp>RNA</scp>‐214 ameliorates hepatic fibrosis and tumor incidence in platelet‐derived growth factor C transgenic mice

Okada, Hikari; Honda, Masao; Campbell, Jean S.; Takegoshi, Kai; Sakai, Yoshio; Yamashita, Taro; Shirasaki, Takayoshi; Takabatake, Riuta; Nakamura, Mikiko; Tanaka, Takuji; Kaneko, Shuichi

doi:10.1111/cas.12730

Cited by 40 publications

(32 citation statements)

References 31 publications

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“…MicroRNA‐214 participated in the development of hepatic fibrosis by modulating the epidermal growth factor receptor and TGF‐β signaling pathways. By using platelet‐derived growth factor‐c transgenic mouse, LNA‐anti‐miR‐214 showed the preventive effect for hepatic fibrosis . Inhibition of miR‐21 also reduced liver fibrosis through concomitant reduction of CD24 + liver progenitor cell and S100 A4 + cancer‐associated stromal cells .…”

Section: Future Therapy For Liver Disease Using Mirnasmentioning

confidence: 99%

MicroRNAs in hepatic pathophysiology

Murakami

Kawada

2016

Hepatology Research

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MicroRNAs (miRNAs) are a group of small non-coding RNAs that range in length from 20 to 25 nucleotides. MicroRNAs are specific for multiple cellular functions, including cell generation, differentiation, multiplication, carcinogenesis, and apoptosis. Many researchers have recently reported that the aberrant expression of miRNAs in hepatic tissue was related to the pathogenesis of liver disease, including viral hepatitis, hepatocellular carcinoma, and fatty liver disease. Multiple studies have proposed that an analysis of circulating miRNAs may be useful for diagnosing etiologies or staging the progression of liver disease, as well as for therapeutic purposes, for example, nucleic acid therapy. This review summarizes and discusses recent advances in the knowledge of miRNAs for chronic liver diseases, with special interest in viral hepatitis, liver fibrosis, and biomarkers.

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Section: Future Therapy For Liver Disease Using Mirnasmentioning

confidence: 99%

MicroRNAs in hepatic pathophysiology

Murakami

Kawada

2016

Hepatology Research

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“…In the progression of HSC activation and hepatic fibrosis, several miRNAs play important role through targeting different mRNAs. Okada found miR‐214 aggravate hepatic fibrosis by decrease the expression of Mig‐6 and increase the levels of EGF‐mediated p‐EGFR 30 . Similarly, miR‐96 can promote hepatic fibrosis in mice by suppressing smad7 31 .…”

Section: Discussionmentioning

confidence: 98%

Identification lncRNA LOC102551149/miR‐23a‐5p pathway in hepatic fibrosis

Zhao

et al. 2020

Eur J Clin Investigation

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Background: Hepatic fibrosis is a worldwide incurable disease; due to the complex and unclear mechanism, there lack the effective therapeutic targets. However, the mechanism of miR-23a-5p underling this pathological process is largely not clear.The purpose of this study was to investigate the role of miR-23a-5p in hepatic fibrosis and HSC activation. Methods: The content of miR-23a-5p in hepatic fibrosis induced by Nnitrosodimethylamine (NDMA) and HSC activation induced by platelet-derived growth factor (PDGF) was detected by qRT-PCR. H&E staining, Masson staining and Shear wave electrography (SWE) were used to detect the degree of hepatic fibrosis. Immunohistochemistry staining, qRT-PCR and Western blot detect the related markers of liver fibrosis or HSC activation, as well as the related pathway genes and proteins. Dual-luciferase reporter system verifies the interaction between miR-23a-5p with PTEN or miR-23a-5p with lncRNA LOC102551149 in HSC-T6. siRNA and miRNA mimic transfer to HSC-T6 to detect the function of lncRNA LOC102551149 and miR-23a-5p on HSC activation. Results: After hepatic fibrosis and HSC activation happened, the expression of miR-23a-5p was up-regulated, whereas anti-miR-23a-5p can alleviate hepatic fibrosis and HSC activation. Further research shows miR-23a-5p can target PTEN and degrade it, causing activation of PI3K/Akt/mTOR/Snail pathway. lncRNA LOC102551149 can be used as a competition endogenous RNA (ceRNA) targeting miR-23a-5p through base pairing, and siRNA LOC102551149 or exogenous miR-23a-5p can induce HSC activation through PI3K/Akt/mTOR/Snail pathway. Conclusion: We demonstrate mechanism pathway of miR-23a-5p on hepatic fibrosis and HSC activation, which may develop a therapeutic target for hepatic fibrosis. K E Y W O R D S hepatic fibrosis, HSC activation, lncRNA LOC102551149, miR-23a-5p, PI3K/Akt, PTEN 2 of 14 | DONG et al.

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“…miRNA-214 appears to participate in the development of liver fibrosis by modulating the epidermal growth factor (EGF) receptor and TGF-β signaling pathways. Also, inhibition of miRNA-214 by locked nucleic acid-antimiRNA-214 ameliorates liver fibrosis in PDGF c transgenic mice [138]. In addition, miRNA-214-5p may play crucial roles in HSC activation and progression of liver fibrosis.…”

Section: Role Of Micrornas (Mirnas) In Liver Pathophysiologymentioning

confidence: 99%

The Promising Role of Anti-Fibrotic Agent Halofuginone in Liver Fibrosis/Cirrhosis

Karakoyun¹

2017

Liver Cirrhosis - Update and Current Challenges

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Liver fibrosis is a complex inflammatory and fibrogenic process that results from chronic liver injury and represents an early step in the progression of cirrhosis. Several cell types [hepatic stellate cells (HSCs), hepatocytes, liver sinusoidal endothelial cells (LSECs), and Kupffer cells (KCs)], cytokines [platelet-derived growth factor (PDGF), transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, interferons (IFNs), interleukins (ILs)], oxidative stress, and microRNAs (miRNAs) are involved in the initiation and progression of liver fibrosis/cirrhosis. Generally, liver fibrosis begins with the stimulation of inflammatory immune cells to secrete cytokines, growth factors, and other activator molecules. These chemical mediators direct HSCs to activate and synthesize large amounts of extracellular matrix (ECM) components. Therefore, HSC activation is a pivotal event in the development of fibrosis and a major contributor to collagen (specifically type I) accumulation. The inhibitory effect of halofuginone on collagen type α1(I) synthesis and ECM deposition has been shown in several experimental models of fibrotic diseases. Halofuginone inhibits TGF-β-induced phosphorylation of Smad3, which is a key phenomenon in the fibrogenesis. It also regulates cell growth and differentiation, apoptosis, cell migration, and immune cell function in liver fibrosis/cirrhosis. This review discusses the etiology and mechanisms of liver fibrosis/cirrhosis and the promising role of antifibrotic agent halofuginone.

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Inhibition of microRNA‐214 ameliorates hepatic fibrosis and tumor incidence in platelet‐derived growth factor C transgenic mice

Cited by 40 publications

References 31 publications

MicroRNAs in hepatic pathophysiology

MicroRNAs in hepatic pathophysiology

Identification lncRNA LOC102551149/miR‐23a‐5p pathway in hepatic fibrosis

The Promising Role of Anti-Fibrotic Agent Halofuginone in Liver Fibrosis/Cirrhosis

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