Abstract:
:Peritoneal fibrosis and loss of transport function is a common complication contributing to adverse outcomes in patients on long-term peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) in mesothelial cells is a salient feature, but its triggering mechanisms remain obscure. Dysregulation of microRNA (miR) expression is implicated in EMT and tissue fibrosis. We investigated the role of miR-200c in EMT and fibrogenesis in a murine PD model and in cultured peritoneal mesothelial cells. PD-fluid-treated mice showed peritoneal miR-200c expression reduced by 76.2% compared with PBS-treated mice, and this was accompanied by increased peritoneal α-smooth muscle actin, fibronectin, and collagen expression. PD fluid and TGF-β1 both reduced miR-200c expression in cultured mesothelial cells, accompanied by downregulation of E-cadherin and decorin, and induction of fibronectin, collagen I and III, and transcription factors related to EMT. Decorin prevented the suppression of miR-200c by TGF-β1. Lentivirus-mediated miR-200c overexpression prevented the induction of fibronectin, collagen I, and collagen III by TGF-β1, independent of decorin, and partially prevented E-cadherin suppression by TGF-β1. Target genes of miR-200c were identified as ZEB2 and Notch1. Our data demonstrate that miR-200c regulates EMT and fibrogenesis in mesothelial cells, and loss of peritoneal miR-200c contributes to PD-associated peritoneal fibrosis.
journal_name
Mol Ther Nucleic Acidsjournal_title
Molecular therapy. Nucleic acidsauthors
Chu JYS,Chau MKM,Chan CCY,Tai ACP,Cheung KF,Chan TM,Yung Sdoi
10.1016/j.omtn.2019.05.008subject
Has Abstractpub_date
2019-09-06 00:00:00pages
78-91issn
2162-2531pii
S2162-2531(19)30138-6journal_volume
17pub_type
杂志文章abstract::E-selectin is an adhesion molecule expressed on the luminal surface of inflamed blood vessels that mediates hematogenous metastasis by assisting shear-resistant adhesion of circulating tumor cells to the vessel surface under dynamic blood flow. Previously, we developed an E-selectin antagonistic thioaptamer (ESTA) for...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.103
更新日期:2016-12-13 00:00:00
abstract::Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the de...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2012.30
更新日期:2012-08-14 00:00:00
abstract::Transactivation of inflammatory and immune mediators in asthma is tightly regulated by nuclear factor κB (NF-κB) and signal transducer and activator of transcription 6 (STAT6). Therefore, we investigated the efficacy of simultaneous inhibition of NF-κB and STAT6 using a chimeric decoy strategy to prevent asthma exacer...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.12.005
更新日期:2018-03-02 00:00:00
abstract::Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a num...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2015.11
更新日期:2015-04-28 00:00:00
abstract::Aberrant insulin-like growth factor I receptor (IGF1R) signaling pathway serves as a well-established target for cancer drug therapy. The intragenic antisense long noncoding RNA (lncRNA) IRAIN, a putative tumor suppressor, is downregulated in breast cancer cells, while IGF1R is overexpressed, leading to an abnormal IG...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.04.013
更新日期:2018-09-07 00:00:00
abstract::The melanoma cell adhesion molecule (MCAM) is involved in melanoma development and its progression, including invasiveness, metastatic potential and angiogenesis. Therefore, MCAM represents a potential target for gene therapy of melanoma, whose expression could be hindered with posttranscriptional specific gene silenc...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2014.56
更新日期:2014-10-28 00:00:00
abstract::Clinical translation of small interfering RNA (siRNA) nanocarriers is hindered by limited knowledge regarding the parameters that regulate interactions between nanocarriers and biological systems. To address this, we investigated the influence of polycation-based nanocarrier architecture on intracellular siRNA deliver...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.05.008
更新日期:2018-09-07 00:00:00
abstract::Recent studies have shown the effect of microRNAs on HSC activation and transformation, which is essential for the pathogenesis of liver fibrosis. In our study, we explored the role of miR-185 in liver fibrosis. Plasma miR-185 was detected in hepatitis B virus-related liver fibrosis patients (S2/3, n = 10) by Illumina...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.11.010
更新日期:2018-03-02 00:00:00
abstract::MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that are primarily considered to be post-transcriptional negative regulators of gene expression acting in the cytoplasm. Over a decade of research has focused on this canonical paradigm of miRNA function, with many success stories. Indeed, miRNAs have been id...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2014.40
更新日期:2014-08-19 00:00:00
abstract::Apoptosis and calcification of endplate chondrocytes (EPCs) can exacerbate intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes (MSC-exosomes) are reported to have the therapeutic potential in IVDD. However, the effects and related mechanisms of MSC-exosomes on EPCs are still unclear. We aim...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.09.026
更新日期:2020-09-26 00:00:00
abstract::The RNA-guided, modified type II prokaryotic CRISPR with CRISPR-associated proteins (CRISPR/Cas9) system represents a simple gene-editing platform with applications in biotechnology and also potentially as a therapeutic modality. The system requires a small guide RNA (sgRNA) and a catalytic Cas9 protein to induce non-...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.01.004
更新日期:2020-03-06 00:00:00
abstract::Cardiomyocyte differentiation derived from embryonic stem cells (ESCs) is a complex process involving molecular regulation of multiple levels. In this study, we first identify and compare differentially expressed gene (DEG) signatures of ESC-derived cardiomyocyte differentiation (ESCDCD) in humans and mice. Then, the ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.011
更新日期:2020-09-04 00:00:00
abstract::PCTAIRE1/CDK16/PCTK1 plays critical roles in cancer cell proliferation and antiapoptosis. To advance our previously published in vitro results with PCTAIRE1 silencing, we examined the in vivo therapeutic potential of this approach by using small interfering RNA (siRNA) encapsulated by lipid nanoparticles. Therapy expe...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.40
更新日期:2016-06-28 00:00:00
abstract::Nonviral vector systems are used increasingly in gene targeting and gene transfer applications. The piggyBac transposon represents an alternative integrating vector for in vivo gene transfer. We hypothesized that this system could achieve persistent gene transfer to the liver when administered systemically. We report ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2012.12
更新日期:2012-10-16 00:00:00
abstract::As a diverse and abundant class of endogenous RNAs, circular RNAs (circRNAs) participate in processes including cell proliferation and apoptosis. Nevertheless, few researchers have investigated the function of circRNAs in bovine muscle development. Based on existing sequencing data, we identified circINSR. The localiz...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.12.032
更新日期:2020-03-06 00:00:00
abstract::Ischemia-reperfusion (I/R) injury is a major side effect of the reperfusion treatment of the ischemic heart. Few therapies are available for the effective prevention of this injury caused by the oxidative stress-induced cardiomyocyte apoptosis. Metformin was shown to have a potential cardiac protective effect and abil...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.09.001
更新日期:2018-12-07 00:00:00
abstract::Human spermatogonial stem cells (SSCs) could have significant applications in reproductive medicine and regenerative medicine because of their great plasticity. The fate determinations of human SSCs are mediated by epigenetic factors. However, nothing is known about the regulation of non-coding RNA on human SSCs. Here...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.05.015
更新日期:2018-09-07 00:00:00
abstract::MicroRNAs (miRNAs) are small noncoding RNAs approximately 20-25 nt in length, which play crucial roles through directly binding to corresponding 3' UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in ha...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章,评审
doi:10.1016/j.omtn.2016.11.003
更新日期:2017-03-17 00:00:00
abstract::Anti-microRNA oligonucleotides (AMOs) are steric blocking antisense reagents that inhibit microRNA (miRNA) function by hybridizing and repressing the activity of a mature miRNA. First generation AMOs employed 2'-O-Methyl RNA nucleotides (2'OMe) with phosphorothioate (PS) internucleotide linkages positioned at both end...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2013.46
更新日期:2013-08-27 00:00:00
abstract::N4-acetylcytidine (ac4C) is often considered to be a conservative, chemically modified nucleoside present on tRNA and rRNA. Recent studies have shown extensive ac4C modifications in human and yeast mRNAs. ac4C helps to correctly read codons during translation and improves translation efficiency and the stability of mR...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章,评审
doi:10.1016/j.omtn.2020.01.037
更新日期:2020-06-05 00:00:00
abstract::Long noncoding RNAs (lncRNAs), which serve as important and powerful regulators of various biological activities, have gained widespread attention in recent years. Emerging evidence has shown that some lncRNAs play important regulatory roles in osteoblast differentiation of mesenchymal stem cells (MSCs), suggesting a ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.03.004
更新日期:2018-06-01 00:00:00
abstract::Bone marrow-derived mesenchymal stem cells (BMSCs) have been suggested to possess the capacity to differentiate into different cell lineages. Maintaining a balanced stem cell differentiation program is crucial to the bone microenvironment and bone development. MicroRNAs (miRNAs) have played a critical role in regulati...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.06.023
更新日期:2019-09-06 00:00:00
abstract::As key regulators of gene expression, microRNAs (miRNAs) have emerged as targets in basic experimentation and therapy. Administration of DNA-encoded RNA molecules, targeting miRNAs through base pairing, is one viable strategy for inhibiting specific miRNAs. A naturally occurring circular RNA (circRNA), ciRS-7, serving...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.09.009
更新日期:2018-12-07 00:00:00
abstract::Septic shock with heart dysfunction is very common in intensive care units. However, whether long noncoding RNA (lncRNA) and mRNA profiles differ between patients with and without myocardial depression is unknown. We generated rat models of hypodynamic septic shock induced by lipopolysaccharide. A total of 12 rat mode...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.07.020
更新日期:2019-09-06 00:00:00
abstract::Development of DNA aptamer screens that are both simple and informative can increase the success rate of DNA aptamer selection and induce greater adoption. High eIF4e levels contribute to malignancies, thus eIF4e presents itself as a valuable target for DNA aptamer-based inhibition screen. Here, we demonstrate a metho...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2014.70
更新日期:2014-12-16 00:00:00
abstract::Thanks to their ability to recognize biomolecular targets with high affinity and specificity, nucleic acid aptamers are increasingly investigated as diagnostic and therapeutic tools, particularly when their targets are cell-surface receptors. Here, we investigate the relationship between the folding of an anti-mouse t...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2013.71
更新日期:2014-01-28 00:00:00
abstract::MicroRNAs (miRNAs) are an important class of small noncoding RNA molecules that serve as excellent biomarkers of various diseases. However, current miRNA biomarkers, including those comprised of multiple miRNAs, work at a single-miRNA level but not at a miRNA-set level, which is defined as a group of miRNAs sharing co...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.004
更新日期:2020-09-04 00:00:00
abstract::Reactivation of γ-globin expression has been shown to ameliorate disease phenotypes associated with mutations in the adult β-globin gene, including sickle cell disease. Specific mutations in the promoter of the γ-globin genes are known to prevent repression of the genes in the adult and thus lead to hereditary persist...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.85
更新日期:2016-10-18 00:00:00
abstract::Recent reports underscore the unparalleled potential of antisense-oligonucleotide (ASO)-based approaches to ameliorate various pathological conditions. However, in vivo studies validating the effectiveness of a short ASO (<10-mer) in the context of a human disease have not been performed. One disease with proven amena...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2014.23
更新日期:2014-07-08 00:00:00
abstract::The fluorescent quantum dots (QDs) delivered small interfering RNAs (siRNAs) targeting β-secretase (BACE1) to achieve high transfection efficiency of siRNAs and reduction of β-amyloid (Aβ) in nerve cells. The CdSe/ZnS QDs with the conjugation of amino-polyethylene glycol (PEG) were synthesized. Negatively charged siRN...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2012.11
更新日期:2012-04-24 00:00:00