Loss of expression of miR-335 is implicated in hepatic stellate cell migration and activation

Chen, Chao; Wu, Chaoqun; Zhang, Zongqi; Yao, Dengfu; Zhu, Liang

doi:10.1016/j.yexcr.2011.05.001

Cited by 83 publications

(57 citation statements)

References 24 publications

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“…Our previous miRNA microarray results showed that miR-126 was significantly decreased during HSCs activation [11], which was consistent with others' researches. However this has not yet been confirmed by qRT-PCR and the role of miR-126 during HSCs activation has not been studied at present.…”

Section: Introductionsupporting

confidence: 90%

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Overexpression of miR-126 Inhibits the Activation and Migration of HSCs through Targeting CRK

Gong

Chen

Hou

et al. 2014

Cell Physiol Biochem

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Background & Aims: MicroRNAs (miRNAs) have been shown to play essential roles in HSCs activation which contributes to hepatic fibrosis. Our previous miRNA microarray results suggested that miR-126 might be decreased during HSCs activation as other studies. The aim of this study is to investigate the role of miR-126 during HSCs activation. Methods: In this study, the expression of miR-126 during HSCs activation was measured and confirmed by qRT-PCR. Then, miR-126 expression was restored by transfection of lentivirus vector encoding miR-126. Futhermore, cell proliferation was assayed by the cell counting kit-8 (CCK-8), cell migration was assayed by transwell assay, and the markers of activation of HSCs, α-SMA and collagen type I, were assayed by qRT-PCR, Western Blotting, Immunostaining and ELISA. Luciferase reporter assay was used to find the target of miR-126, and Western Blotting and Immunostaining was used to validate the target of miR-126. Then, the expression and the role of the target of miR-126 during HSCs activation was further assessed. Results: The expression of miR-126 was confirmed to be significantly decreased during HSCs activation. Overexpression of miR-126 significantly inhibited HSCs migration but did not affect HSCs proliferation. The expression of α-SMA and collagen type I were both obviously decreased by miR-126 restoration. CRK was found to be the target of miR-126 and overexpression of miR-126 significantly inhibited CRK expression. And it was found that overexpression of CRK also significantly decreased miR-126 expression and promoted HSCs activation. Conclusions: Our study showed that overexpression of miR-126 significantly inhibited the activation and migration of HSCs through targeting CRK which can also decrease miR-126 expression and promote HSCs activation.

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Section: Introductionsupporting

confidence: 90%

“…Primary rat HSC were isolated from the livers through two steps of digestion as our previously research did [11]. …”

Section: Methodsmentioning

confidence: 99%

Overexpression of miR-126 Inhibits the Activation and Migration of HSCs through Targeting CRK

Gong

Chen

Hou

et al. 2014

Cell Physiol Biochem

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“…miR-335 targets tenascin-C (TN-C), extracellular matrix glycoprotein upregulated in liver fibrosis and promotes HSC migration and activation via integrin β1. Overexpression of miR-335 resulted in a decreased α-SMA and collagen type-I level by decreasing the expression of TNC (105).…”

Section: Mir-335mentioning

confidence: 99%

Delivery and Targeting of miRNAs for Treating Liver Fibrosis

Kumar

Mahato

2014

Pharm Res

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Liver fibrosis is a pathological condition originating from liver damage that leads to excess accumulation of extracellular matrix (ECM) proteins in the liver. Viral infection, chronic injury, local inflammatory responses and oxidative stress are the major factors contributing to the onset and progression of liver fibrosis. Multiple cell types and various growth factors and inflammatory cytokines are involved in the induction and progression of this disease. Various strategies currently being tried to attenuate liver fibrosis include the inhibition of HSC activation or induction of their apoptosis, reduction of collagen production and deposition, decrease in inflammation, and liver transplantation. Liver fibrosis treatment approaches are mainly based on small drug molecules, antibodies, oligonucleotides (ODNs), siRNA and miRNAs. MicroRNAs (miRNA or miR) are endogenous noncoding RNA of ~22 nucleotides that regulate gene expression at post transcription level. There are several miRNAs having aberrant expressions and play a key role in the pathogenesis of liver fibrosis. Single miRNA can target multiple mRNAs, and we can predict its targets based on seed region pairing, thermodynamic stability of pairing and species conservation. For in vivo delivery, we need some additional chemical modification in their structure, and suitable delivery systems like micelles, liposomes and conjugation with targeting or stabilizing the moiety. Here, we discuss the role of miRNAs in fibrogenesis and current approaches of utilizing these miRNAs for treating liver fibrosis.

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“…12,16,17 This comprehensive change in gene expression is associated with a pronounced dysregulation of miRNA synthesis. [18][19][20] Recent studies have shown that several miRNA, such as miR-16, 21 miR-27a/b, 20 miR-195, 22 and miR-335 23 are involved in proliferation or induced migration of myofibroblastic-activated HSC. Others such as miR-19b, miR-150, and miR-194 are suggested to participate in TGF-b signaling and myofibroblastic HSC activation, respectively.…”

mentioning

confidence: 99%

Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29

Kwiecinski

Elfimova

Noetel

et al. 2012

Laboratory Investigation

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Loss of expression of miR-335 is implicated in hepatic stellate cell migration and activation

Cited by 83 publications

References 24 publications

Overexpression of miR-126 Inhibits the Activation and Migration of HSCs through Targeting CRK

Overexpression of miR-126 Inhibits the Activation and Migration of HSCs through Targeting CRK

Delivery and Targeting of miRNAs for Treating Liver Fibrosis

Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29

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