Positive regulation of hepatic miR-122 expression by HNF4α

Li, Zhen‐Ya; Yang, Xi; Zhu, Wen-Nan; Zeng, Chao; Zhang, Zhu-Qin; Guo, Zengjun; Hao, Dejun; Guang, Liu; Feng, Lei; Chen, Hou-Zao; Chen, Feng; Lv, Xiang; Liu, De-Pei; Liang, Chih‐Chuan

doi:10.1016/j.jhep.2010.12.023

Cited by 133 publications

(149 citation statements)

References 39 publications

Supporting

Mentioning

137

Contrasting

Unclassified

Order By: Relevance

“…Due to their regulatory nature, microRNAs are often tissue specific and with that knowledge miR-122 can be used as a hepatocyte-specific promoter [73]. As one might expect, the expression of a hepatic upregulated microRNA, miR-122a, can also be exploited in the reverse fashion, namely by inserting a microRNA target site in the 3ʹ UTR region of the gene therapy transgene, effectively preventing transgene expression in hepatocytes but retaining expression in the sinusoidal endothelial cells [74].…”

Section: A Brief History Of In-vivo Gene Therapymentioning

confidence: 99%

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Haasteren

Hyde

Gill

2018

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Introduction: Ex-vivo gene therapy has had significant clinical impact over the last couple of years and in-vivo gene therapy products are being approved for clinical use. Gene therapy and gene editing approaches have huge potential to treat genetic disease and chronic illness. Areas covered: This article provides a review of in-vivo approaches for gene therapy in the lung and liver, exploiting non-viral and viral vectors with varying serotypes and pseudotypes to target-specific cells. Antibody responses inhibiting viral vectors continue to constrain effective repeat administration. Lessons learned from ex-vivo gene therapy and genome editing are also discussed. Expert opinion: The fields of lung and liver in-vivo gene therapy are thriving and a comparison highlights obstacles and opportunities for both. Overcoming immunological issues associated with repeated administration of viral vectors remains a key challenge. The addition of targeted small molecules in combination with viral vectors may offer one solution. A substantial bottleneck to the widespread adoption of in-vivo gene therapy is how to ensure sufficient capacity for clinical-grade vector production. In the future, the exploitation of gene editing approaches for in-vivo disease treatment may facilitate the resurgence of non-viral gene transfer approaches, which tend to be eclipsed by more efficient viral vectors.

show abstract

Section: A Brief History Of In-vivo Gene Therapymentioning

confidence: 99%

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Haasteren

Hyde

Gill

2018

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

show abstract

“…Expression of miR-122 is regulated by a number of transcription factors including hepatocyte nuclear factors HNF1α, HNF3β, HNF4α and by C/EBPα [9][10][11] (CAAT/enhancer-binding protein). MiR-122 expression was also shown to be epigenetically regulated by the PPARγ/RXRa complex 12 .…”

Section: A C C E P T E Dmentioning

confidence: 99%

Inflammation-Induced Expression and Secretion of MicroRNA 122 Leads to Reduced Blood Levels of Kidney-Derived Erythropoietin and Anemia

et al. 2016

View full text Add to dashboard Cite

BACKGROUND AIM Anemia is commonly associated with acute and chronic inflammation, but the mechanisms of their interaction are not clear. We investigated whether microRNA 122 (MIR122), which is generated in the liver and is secreted into the blood, is involved in the development of anemia associated with inflammation. METHODS We characterized the primary transcript of the human liverspecific MIR122 using northern blot, quantitative real-time PCR, and 3' and 5' RACE analyses. We studied regulation of MIR122 in human hepatocellular carcinoma (HCC) cell lines (Huh7 and HepG2) as well as in C57BL/6 and mice with disruption of the tumor necrosis factor gene (Tnf). Liver tissues were collected and analyzed by bioluminescence imaging or immunofluorescence. Inflammation in mice was induced by lipopolysaccharide (LPS) or by cerulein injections. Mice were given 4 successive injections of LPS, leading to inflammation-induced anemia. Steatohepatitis was induced with a choline-deficient high-fat diet. Hemolytic anemia was stimulated by phenylhydrazine injection. MIR122 was inhibited in mice by tail-vein injection of antogomiR-122 (an oligonucleotide antagonist of MIR122). MicroRNA and mRNA levels were determined by quantitative real time PCR. RESULTS The primary transcript of MIR122 spanned 5 kb, comprising 3 exons; the third encodes MIR122. Within the MIR122 promoter region we identified a nuclear factor-B (NF-B) binding site and demonstrated that RELA, as well as activators of NF-B (TNF and LPS), increased promoter activity of MIR122. Administration of LPS to mice induced secretion of MIR122 into blood, which required TNF. Secreted MIR122 reached the kidney and reduced expression of erythropoietin (Epo), which we identified as a MIR122 target gene. Injection of mice with antagomiR-122 increased blood levels of EPO, reticulocytes, and hemoglobin. We found an inverse relationship between blood levels of MIR122 and EPO in mice with acute pancreatitis or steatohepatitis, and also in patients with acute inflammation. CONCLUSION In mice, we found that LPS-induced inflammation increases blood levels of MIR122, which reduces expression of Epo in the kidney; this is a mechanism of inflammation-induced anemia. Strategies to block MIR122 in patients with inflammation could reduce the development or progression of anemia. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT AbstractBackground & Aim: Anemia is commonly associated with acute and chronic inflammation, but the mechanisms of their interaction are not clear. We investigated whether microRNA 122 (MIR122),...

show abstract

“…Like mRNAs, miRNA expression is controlled at the transcriptional level by gene-specific transcription factors (Li et al, 2011d;Wang et al, 2011). miRNA expression can also be regulated by epigenetic mechanisms.…”

Section: Biogenesis Of Mirnasmentioning

confidence: 99%

MicroRNAs in farm animals

Wang

Jiang

2013

Animal

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are a class of ,22 nucleotide-long small noncoding RNAs that target mRNAs for translational repression or degradation. miRNAs target mRNAs by base-pairing with the 3 0 -untranslated regions (3 0 -UTRs) of mRNAs. miRNAs are present in various species, from animals to plants. In this review, we summarize the identification, expression, and function of miRNAs in four important farm animal species: cattle, chicken, pig and sheep. In each of these species, hundreds of miRNAs have been identified through homology search, small RNA cloning and next generation sequencing. Real-time RT-PCR and microarray experiments reveal that many miRNAs are expressed in a tissue-specific or spatiotemporal-specific manner in farm animals. Limited functional studies suggest that miRNAs have important roles in muscle development and hypertrophy, adipose tissue growth, oocyte maturation and early embryonic development in farm animals. Increasing evidence suggests that single-nucleotide polymorphisms in miRNA target sites or miRNA gene promoters may contribute to variation in production or health traits in farm animals.

show abstract

Positive regulation of hepatic miR-122 expression by HNF4α

Cited by 133 publications

References 39 publications

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Inflammation-Induced Expression and Secretion of MicroRNA 122 Leads to Reduced Blood Levels of Kidney-Derived Erythropoietin and Anemia

MicroRNAs in farm animals

Contact Info

Product

Resources

About