ArticleThe Journal of biological chemistry2016
Suppressor of Cytokine Signaling-3 (SOCS-3) Induces Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Expression in Hepatic HepG2 Cell Line.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- The Role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Cardiovascular Homeostasis: A Non-Systematic Literature Review.Current cardiology reviews · 2017Pooled it
- The Impact of PCSK9 Inhibitors on Circulatory Inflammation: Mechanisms, Evidence, and Application Prospects.JACC. Asia · 2026Review
- Selected Nutraceuticals in Metabolic Syndrome: Molecular Mechanisms and Clinical Implications.Biomedicines · 2026Review
- Transforming growth factor beta reduces proprotein convertase subtilisin/kexin type 9 in the supernatant of hepatic stellate cells.World journal of hepatology · 2026Article
- Computational-experimental study reveals direct target and bioactives of Ajania fruticulosa against NAFLD via TLR2/NF-κB/PPAR-γ signaling.NPJ science of food · 2026Article
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's Disease: Recent Advances and Controversies.Molecular neurobiology · 2025Review
- Regulatory mechanisms of hepatocyte PCSK9 expression: translating mechanistic insights into potential nutraceuticals.Chinese medicine · 2025Review
- DNA methylation patterns and predictive models for metabolic disease risk in offspring of gestational diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- PCSK9 Manipulates Lipid Metabolism and the Immune Microenvironment in Cancer.OncoTargets and therapy · 2025Review
- Relationship of the metabolic score for insulin resistance and the new-onset hypertension: Evidence from CHARLS.PloS one · 2025Article
- PCSK9 in T-cell function and the immune response.Biomarker research · 2024Review
- Genetic association of lipid and lipid-lowering drug target genes with atopic dermatitis: a drug target Mendelian randomization study.Scientific reports · 2024Article
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Prognostic Value ofCancers · 2024Article
- Unveiling Novel Protein Biomarkers for Psoriasis Through Integrated Analysis of Human Plasma Proteomics and Mendelian Randomization.Psoriasis (Auckland, N.Z.) · 2024Article
- Article
- DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.Nature communications · 2023Article
- Targeting PCSK9 reduces cancer cell stemness and enhances antitumor immunity in head and neck cancer.iScience · 2023Article
- Review
- PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The suppressor of cytokine signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway activated by proinflammatory cytokines, including the tumor necrosis factor-α (TNF-α). SOCS3 is also implicated in hypertriglyceridemia associated to insulin resistance. Proprotein convertase subtilisin kexin type 9 (PCSK9) levels are frequently found to be positively correlated to insulin resistance and plasma very low density lipoprotein (VLDL) triglycerides concentrations. The present study aimed to investigate the possible role of TNF-α and JAK/STAT pathway on de novo lipogenesis and PCSK9 expression in HepG2 cells. TNF-α induced both SOCS3 and PCSK9 in a concentration-dependent manner. This effect was inhibited by transfection with siRNA anti-STAT3, suggesting the involvement of the JAK/STAT pathway. Retroviral overexpression of SOCS3 in HepG2 cells (HepG2(SOCS3)) strongly inhibited STAT3 phosphorylation and induced PCSK9 mRNA and protein, with no effect on its promoter activity and mRNA stability. Consistently, siRNA anti-SOCS3 reduced PCSK9 mRNA levels, whereas an opposite effect was observed with siRNA anti-STAT3. In addition, HepG2(SOCS3) express higher mRNA levels of key enzymes involved in the de novo lipogenesis, such as fatty-acid synthase, stearoyl-CoA desaturase (SCD)-1, and apoB. These responses were associated with a significant increase of SCD-1 protein, activation of sterol regulatory element-binding protein-1c (SREBP-1), accumulation of cellular triglycerides, and secretion of apoB. HepG2(SOCS3) show lower phosphorylation levels of insulin receptor substrate 1 (IRS-1) Tyr(896) and Akt Ser(473) in response to insulin. Finally, insulin stimulation produced an additive effect with SOCS3 overexpression, further inducing PCSK9, SREBP-1, fatty acid synthase, and apoB mRNA. In conclusion, our data candidate PCSK9 as a gene involved in lipid metabolism regulated by proinflammatory cytokine TNF-α in a SOCS3-dependent manner.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.