Aims: Fibroblast growth factor receptor 4 (FGFR4) is a key mediator that protects the liver from chronic injury. MicroRNA-7 (miR-7) is a tumor suppressor and associated with lipid homeostasis in the liver. This study was designed to examine the role of the miR-7-5p/FGFR4 axis in liver fibrogenesis.
Methods: TargetScan was employed to predict microRNAs that targeted FGFR4 on the 3'-untranslated region (3'-UTR). miR-7-5p and FGFR4 expression in pathological liver tissues and LX-2 cells was determined using qRT-PCR and an immunoblotting assay. A dual-luciferase assay was conducted to validate the target prediction. A Cell Counting Lit-8 assay was performed to assess the proliferation ability of LX-2 cells. Hydroxyproline content in LX-2 cells was measured using a hydroxyproline assay. The expression of hepatic stellate cell (HSC) activation markers was examined using qRT-PCR and an immunoblotting assay.
Results: FGFR4 was a putative target of miR-7-5p. In LX-2 cells, miR-7-5p targeted FGFR4 by binding to 3'-UTR. FGFR4 was downregulated, but miR-7-5p was markedly enhanced in the liver samples as the degree of liver fibrosis rose. miR-7-5p was negatively associated with FGFR4 expression in liver tissues. The miR-7-5p inhibitor blocked the lipopolysaccharide-induced proliferation and activation of LX-2 cells, and FGFR4 overexpression inhibited LX-2 cell proliferation and activation triggered by miR-7-5p.
Conclusion: miR-7-5p promotes HSC proliferation and activation by downregulating FGFR4.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303738 | PMC |
http://dx.doi.org/10.1155/2020/5346573 | DOI Listing |
Acta Pharmacol Sin
January 2025
Carbohydrate-Based Drug Research Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
The hepatoprotective effect of the fruit of Lycium barbarum has been documented in China over millennia. Lycium barbarum polysaccharides (LBPs) were the first macromolecules reported to mitigate liver fibrosis in carbon tetrachloride (CCl)-treated mice. Herein, a neutral peptidoglycan, named as LBPW, was extracted from the fruit of Lycium barbarum.
View Article and Find Full Text PDFACS Omega
January 2025
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, 00433 Nablus, Palestine.
Currently, available therapies for diabetes cannot achieve normal sugar values in a high percentage of treated patients. This work synthesized a series of carbazole-triazole-thione derivatives, and their potential antidiabetic activity was investigated against the key diabetic enzymes α-amylase and glycosidase. Normal human hepatic stellate cells (LX-2) were employed to assess their cytotoxicity and safety, followed by in vivo testing to investigate the hypoglycemic effect of the most promising agent.
View Article and Find Full Text PDFEur J Pharmacol
January 2025
College of Korean Medicine, Gachon University, Seongnam, 13120, South Korea. Electronic address:
Obesity due to excessive body fat accumulation remains a global problem. Patients with obesity have high cortisol levels, and its dysregulation is caused by increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) levels. The effects and mechanism of J2H-1702, an 11β-HSD1 inhibitor, on nonalcoholic steatohepatitis (NASH) were explored.
View Article and Find Full Text PDFCurr Drug Deliv
January 2025
School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Molecules
December 2024
Department of Preclinical Sciences, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania.
Metamizole (dipyrone) is a non-opioid analgesic widely used in human and veterinary medicine, despite ongoing concerns about its safety due to risks such as agranulocytosis and potential hepatotoxicity. This study investigates the cytotoxic (MTT assay) and pro-apoptotic effects of metamizole and its primary metabolites, 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA), on the LX-2 liver cell line. These metabolites are implicated in both the therapeutic and adverse effects of the drug.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!