ArticleJournal of cellular and molecular medicine2016
Enhanced pro-protein convertase subtilisin/kexin type 9 expression by C-reactive protein through p38MAPK-HNF1α pathway in HepG2 cells.
Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- HepG2 cells stimulated by THP-1-conditioned medium: a potential in vitro model of systemic inflammation-induced hepatic alterations.Molecular biology reports · 2026Article
- Genetically proxied PCSK9 inhibition is associated with reduced psoriatic arthritis risk.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Association of proprotein convertase subtilisin/kexin type 9 protein and oxidative stress indicators in women with preeclampsia: A case-control study.International journal of reproductive biomedicine · 2023Article
- C-Reactive Protein Signaling Pathways in Tumor Progression.Biomolecules & therapeutics · 2023Review
- Peri-event plasma PCSK9 and hsCRP after an acute myocardial infarction correlate with early deterioration of left ventricular ejection fraction: a cohort study.Lipids in health and disease · 2022Article
- Genome-wide Association Analysis of Proinflammatory Cytokines and Gene-lifestyle Interaction for Invasive Breast Cancer Risk: The WHI dbGaP Study.Cancer prevention research (Philadelphia, Pa.) · 2021Observational
- The Effect of Inflammation and Insulin Resistance on Lipid and Lipoprotein Responsiveness to Dietary Intervention.Current developments in nutrition · 2020Article
- Beneficial impact of epigallocatechingallate on LDL-C through PCSK9/LDLR pathway by blocking HNF1α and activating FoxO3a.Journal of translational medicine · 2020Article
- Methotrexate Decreases the Level of PCSK9-A Novel Indicator of the Risk of Proatherogenic Lipid Profile in Psoriasis. The Preliminary Data.Journal of clinical medicine · 2020Article
- Inflammation Induces Lipid Deposition in Kidneys by Downregulating Renal PCSK9 in Mice with Adriamycin-Induced Nephropathy.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Liraglutide downregulates hepatic LDL receptor and PCSK9 expression in HepG2 cells and db/db mice through a HNF-1a dependent mechanism.Cardiovascular diabetology · 2018Article
- PCSK9 targets important for lipid metabolism.Clinical research in cardiology supplements · 2017Review
- Proprotein Convertase Subtilisin/Kexin 9 Levels in Relation to Systemic Immune Activation and Subclinical Coronary Plaque in HIV.Open forum infectious diseases · 2017Article
- The PCSK9 Protein Is Not Necessarily a Risk Factor for Major Depressive Disorder.Basic and clinical neuroscienceArticle
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasma C-reactive protein (CRP) concentration is associated positively with cardiovascular risk, including dyslipidemia. We suggested a regulating role of CRP on pro-protein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein (LDL) metabolism, and demonstrated the PCSK9 as a pathway linking CRP and LDL regulation. Firstly, experiments were carried out in the presence of human CRP on the protein and mRNA expression of PCSK9 and LDL receptor (LDLR) in human hepatoma cell line HepG2 cells. Treatment with CRP (10 μg/ml) enhanced significantly the mRNA and protein expression of PCSK9 and suppressed the expression of LDLR. Of note, a late return of LDLR mRNA levels occurred at 12 hrs, while the LDLR protein continued to decrease at 24 hrs, suggesting that the late decrease in LDLR protein levels was unlikely to be accounted for the decrease in LDL mRNA. Secondly, the role of PCSK9 in CRP-induced LDLR decrease and the underlying pathways were investigated. As a result, the inhibition of PCSK9 expression by small interfering RNA (siRNA) returned partly the level of LDLR protein and LDL uptake during CRP treatment; CRP-induced PCSK9 increase was inhibited by the p38MAPK inhibitor, SB203580, resulting in a significant rescue of LDLR protein expression and LDL uptake; the pathway was involved in hepatocyte nuclear factor 1α (HNF1α) but not sterol responsive element-binding proteins (SREBPs) preceded by the phosphorylation of p38MAPK. These findings indicated that CRP increased PCSK9 expression by activating p38MAPK-HNF1α pathway, with a certain downstream impairment in LDL metabolism in HepG2 cells.
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