Data di Pubblicazione:
2016
Citazione:
Adipose tissue related adipokines and cytokines regulate PCSK9 expression in HepG2 cells / M. Ruscica, M. Botta, C. Songia, C. Macchi, A. Corsini, P. Magni, N. Ferri. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 186:Suppl 10(2016 Oct). (Intervento presentato al 3rd. convegno Joint Meeting of Pathology and Laboratory Medicine tenutosi a Montesilvano (Pescara) nel 2016).
Abstract:
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) represents a key-regulator
pathway for hepatic LDL receptor degradation. Clinical and experimental evidence indicates that
PCSK9 may be either a cause or an effect of MetS. PCSK9 levels correlate with MetS features,
namely atherogenic dyslipidemia and insulin sensitivity indices. The aim was to study the possible
molecular mechanisms linking the effects of cytokines (TNF-α and resistin) and adipokines (leptin)
on PCSK9 expression and de novo lipogenesis. Methods: Human hepatocellular liver carcinoma cell
line (HepG2) and HepG2 overexpressing PCSK9 (HepG2PCSK9) were used as in vitro tools. qPCR,
Western blot, ELISA and luciferase reporter assays, together with siRNA directed to STAT3 and
SOCS3, were used. Results: HepG2 expresses leptin (ObRl) and resistin (adenylyl cyclaseassociated
protein 1, CAP1) receptors. HepG2PCSK9 expresses higher levels of ObRl and CAP1.
Twenty-four h treatment of HepG2 with TNF-α (10 ng/mL), and 48-h treatment with leptin (200
ng/mL) and resistin (50 ng/mL) induced the expression of both PCSK9 (2.3-, 2.0- and 3.5-fold,
respectively) and SOCS3 (3-, 1.8- and 1.9-fold, respectively). TNF-α and leptin increased the
secreting PCSK9 (+15% and +20%, respectively) but only leptin stimulated PCSK9 promoter activity
(+20%). TNF-α, leptin and resistin induced the gene expression of sterol regulatory elementbinding
protein 1 (SREBP1), stearoyl-CoA desaturase-1 (SCD-1), fatty acid synthase (FAS) and
microsomal triglyceride transfer protein (MTP). The TNF-α mediated effects were inhibited by
transfection with siRNA anti-STAT3, suggesting the involvement of the JAK/STAT pathway.
Conclusions: Pro-inflammatory cytokines and adipokines up-regulate PCSK9 expression and the
key genes involved in the de novo lipogenesis.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
M. Ruscica, M. Botta, C. Songia, C. Macchi, A. Corsini, P. Magni, N. Ferri
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