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1.
Cell Mol Gastroenterol Hepatol ; 13(5): 1393-1412, 2022.
Article in English | MEDLINE | ID: mdl-35093591

ABSTRACT

BACKGROUND & AIMS: Hepatic fibrosis is characterized by hepatic stellate cell (HSC) activation and transdifferentiation-mediated extracellular matrix (ECM) deposition, which both contribute to cirrhosis. However, no antifibrotic regimen is available in the clinic. microRNA-23b/27b/24-1 cluster inhibition of transforming growth factor-ß (TGF-ß) signaling during hepatic development prompted us to explore whether this cluster inhibits HSC activation and hepatic fibrosis. METHODS: Experimental fibrosis was studied in carbon tetrachloride (CCl4)-treated C57BL/6 mice. After administration of miR-23b/27b/24-1 lentivirus or vehicle, animals were euthanized for liver histology. In primary rat HSC and HSC-T6, the anti-fibrotic effect of miR-23b/27b/24-1 cluster was furtherly investigated by RNA-sequencing, luciferase reporter assay, western blotting and bioinformatic means. RESULTS: In this study, we showed that increasing the miR-23b/27b/24-1 level through intravenous delivery of miR-23b/27b/24-1 lentivirus ameliorated mouse hepatic fibrosis. Mechanistically, the miR-23b/27b/24-1 cluster directly targeted messenger RNAs, which reduced the protein expression of 5 secretory profibrotic genes (TGF-ß2, Gremlin1, LOX, Itgα2, and Itgα5) in HSCs. Suppression of the TGF-ß signaling pathway by down-regulation of TGF-ß2, Itgα2, and Itgα5, and activation of the bone morphogenetic protein signaling pathway by inhibition of Gremlin1, decreased extracellular matrix secretion of HSCs. Furthermore, down-regulation of LOX expression softened the ECM. Moreover, a reduction in tissue inhibitors of metalloproteinase 1 expression owing to weakened TGF-ß signaling increased ECM degradation. CONCLUSIONS: Hepatic overexpression of the miR-23b/27b/24-1 cluster blocked hepatic fibrosis and may be a novel therapeutic regimen for patients with hepatic fibrosis.


Subject(s)
Hepatic Stellate Cells , MicroRNAs , Animals , Hepatic Stellate Cells/pathology , Humans , Liver Cirrhosis/chemically induced , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , MicroRNAs/metabolism , Rats , Transforming Growth Factor beta2/metabolism
2.
J Biol Res (Thessalon) ; 28(1): 15, 2021 Jul 16.
Article in English | MEDLINE | ID: mdl-34271975

ABSTRACT

E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed.

3.
Cell Biosci ; 8: 63, 2018.
Article in English | MEDLINE | ID: mdl-30534359

ABSTRACT

Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate gene or protein expression; however, their function in the progression of hepatic fibrosis remains unclear. Hepatic fibrosis is a continuous wound-healing process caused by numerous chronic hepatic diseases, and the activation of hepatic stellate cells (HSCs) is generally considered to be a pivotal step in hepatic fibrosis. In the process of hepatic fibrosis, some lncRNAs regulates diverse cellular processes. Here are several examples: the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and liver fibrosis-associated lncRNA1 (lnc-LFAR1) promote HSC activation in the progression of hepatic fibrosis via the transforming growth factor-ß signaling pathway; the lncRNA HIF 1 alpha-antisense RNA 1 (HIF1A-AS1) and Maternally expressed gene 3 reduce HSC activation which are associated with DNA methylation; the lncRNA plasmacytoma variant translocation 1, Homeobox (HOX) transcript antisense RNA and MALAT1 promote HSC activation as competing endogenous RNAs (ceRNAs); the long intergenic non-coding RNA-p21 (lncRNA-p21) and Growth arrest-specific transcript 5 reduce HSC activation as ceRNAs. As we get to know more about the function of lncRNAs in hepatic fibrosis, more and more ideas for the molecular targeted therapy in hepatic fibrosis will be put forward.

4.
Anal Chim Acta ; 854: 202-8, 2015 Jan 07.
Article in English | MEDLINE | ID: mdl-25479885

ABSTRACT

A fluorescent polymer dots positive readout and sensitive lateral flow assay (LFA) based on fluorescent quenching has been developed to detect ractopamine (Rac), a chemical residue in food, harmful to human health. Compared with traditional LFA strips, these fluorescent quenching LFA (FQLFA) strips provide a positive correlation method that allows users to obtain results from a weak fluorescent signal. The immunoassay strip scheme is based on the fact that fluorescent polymer dots (FPDs) in close proximity to gold nanoparticles (AuNPs) represent a strong fluorescent quenching. We show that the FQLFA strips can be used as a source to quantitatively analyze Rac in phosphate buffers (PB), swine urine and muscle tissue samples. The lowest detection limitation of the FQLFA was 0.16 ng mL(-1). Our results indicated that this novel scheme was more suitable for rapid detection of small molecules.


Subject(s)
Fluorescent Dyes/chemistry , Phenethylamines/chemistry , Animals , Swine
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