Background: Hepatocyte apoptosis plays an important role in the progression of liver fibrosis. Overexpression of HGF (Hepatocyte growth factor) can reduce hepatocyte apoptosis and alleviate liver fibrosis. Our study aims to investigate whether resveratrol (Res) can alleviate liver fibrosis through miR-190a-5p /HGF axis.
Methods: The TGF-β1 (transforming growth factor-β1)-induced primary hepatocyte model in vitro and CCl-induced liver fibrosis model in vivo were established. Hepatocyte apoptosis was determined by flow cytometry and TdT-mediated dUTP nick-end labeling (TUNEL) assay. HE (hematoxylin and eosin) staining and Sirius red staining were performed to observe the pathological changes of the liver tissues. Western blotting was used to determine the expression of apoptosis-associated proteins and HGF. Quantitative Real-time PCR (QRT-PCR) was used to quantify miR-190a-5p expression. The dual-luciferase reporter assay was performed to verify the targeting relationship between miR-190a-5p and HGF.
Results: Hepatocyte apoptosis and miR-190a-5p expression level were increased in TGF-β1-induced cell models in vitro while the results were reversed after treatment with Res. Besides, miR-190a-5p negatively regulated HGF expression, and miR-190a-5p regulated hepatocyte apoptosis by targeting HGF. Res reduced the apoptosis of hepatocytes and the effect was achieved by decreasing the expression levels of miR-190a-5p and increasing HGF expression in vitro. Moreover, experiments in vivo verified that Res reduced apoptosis of the hepatocytes reduced AST, and ALT levels, as well as raised Albumin levels in the serum. Apart from that, Res decreased the expression ofmiR-190a-5p and increased HGF levels at the same time, and further reduced liver fibrosis.
Conclusion: In summary, our study indicated that Res could inhibit the up-regulation of miR-190a-5p caused by CCl or TGF-β1. And then the decreased miR-190a-5p could further lessen the hepatocyte apoptosis by increasing HGF levels and finally relieving liver fibrosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2021.116593 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Design, Synthesis, and Cytotoxicity Evaluation of Novel Indolin-2-One Based Molecules on Hepatocellular Carcinoma HepG2 Cells as Protein Kinase Inhibitors.
Molecules
February 2025
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
A series of indolinone-based derivatives were designed and synthesized using the hybrid pharmacophoric design approach as cytotoxic kinase inhibitors. The cytotoxic effects of the designed molecules were tested against MCF-7 and HepG-2 cell lines. Compounds and were the most cytotoxic, with IC values against HepG-2 and MCF-7 cells ranging from 2.
View Article and Find Full Text PDFFaberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms.
Molecules
February 2025
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China.
Cancer remains a significant global public health challenge, with hepatocellular carcinoma (HCC) ranking among the top five malignancies in terms of mortality. Faberidilactone A, a sesquiterpenoid dimer isolated from , exhibits potent cytotoxicity against various human tumor cell lines and demonstrates remarkable antitumor potential. In vitro studies using HepG2 cells revealed that faberidilactone A induces apoptosis and ferroptosis, causes cell cycle arrest, enhances the production of intracellular reactive oxygen species (ROS), and disrupts mitochondrial function.
View Article and Find Full Text PDFEffects and potential pathways of goose astrovirus infection on gosling hepatic lipid metabolism.
Front Microbiol
February 2025
Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
Introduction: The adverse effects of goose astrovirus (GoAstV) on avian growth and health have been widely reported previously, while the stress reactions and corresponding mechanism of gosling liver responding to GoAstV infection remain not entirely clear.
Methods: One-day-old goslings inoculated subcutaneously with 2 × 10 TCID of GoAstV were employed as an experimental model, and the potential effects and pathways of GoAstV infection on gosling liver functions were investigated by combining the morphological, biochemical and RNA sequencing (RNA-seq) techniques.
Results: Structural and functional impairments were found in gosling livers post the virus infection, as characterized by the histological alterations in liver index and morphology of hepatic cord and sinuses, as well as the abnormal expression patterns of the cellular antioxidant, inflammation and apoptosis-related genes.
VDAC2 and Bak scarcity in liver mitochondria enables targeting hepatocarcinoma while sparing hepatocytes.
Nat Commun
March 2025
MitoCare Center, Department of Pathology and Genomic Medicine and Thomas Jefferson University, Philadelphia, PA, USA.
Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity.
View Article and Find Full Text PDFSynthesis and antitumor evaluation of amino acid conjugates of monocarbonyl curcumin in hepatocellular carcinoma cell.
Sci Rep
March 2025
College of Public Health, Anhui University of Science and Technology, Hefei, 230000, China.
Curcumin possesses a variety of pharmacological properties, particularly anticancer activity. However, its clinical utility is limited by its poor water solubility and low bioavailability. To alleviate the problems, our previous research demonstrated that mono-carbonyl curcumin easters can be employed for the development of novel anticancer agents.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!