Suppressor of cytokine signaling-3 (SOCS-3) induces proprotein convertase subtilisin kexin type 9 (PCSK9) expression in hepatic hepg2 cell line
Poster
Data di Pubblicazione:
2015
Citazione:
Suppressor of cytokine signaling-3 (SOCS-3) induces proprotein convertase subtilisin kexin type 9 (PCSK9) expression in hepatic hepg2 cell line / C. Ricci, M. Ruscica, C. Macchi, P. Magni, R. Cristofani, J. Liu, A. Corsini, N. Ferri. - In: GIORNALE ITALIANO DELL'ARTERIOSCLEROSI. - ISSN 2240-4821. - 6:4(2015 Nov 22), pp. 44-44. ((Intervento presentato al 29. convegno Società Italiana per lo Studio della Aterosclerosi (SISA) tenutosi a Bologna nel 2015.
Abstract:
The suppressor of cytokine signaling (SOCS) proteins are negative
regulators of the JAK/STAT pathway activated by pro-inflammatory
cytokines, including the tumor necrosis factor-α (TNF-a).
SOCS3 is also implicated in hypertriglyceridemia associated to
insulin-resistance (IR).
Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) levels are
frequently found to be positively correlated to IR and plasma very
low-density lipoprotein-triglycerides (VLDL-TG) 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-a 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 (HepG2SOCS3) strongly
inhibited STAT3 phosphorylation and induced PCSK9 mRNA and
protein, with no effect on its promoter activity. Consistently, siRNA
anti-SOCS3 reduced PCSK9 mRNA levels while an opposite effect
was observed with siRNA anti-STAT3. In addition, HepG2SOCS3 express
higher mRNA levels of key enzymes involved in the de novo
lipogenesis, such as fatty-acid synthase (FAS), stearoyl-CoA desaturase,
and apo-B.
These responses were associated with significant increase of SCD-
1 protein, activation of SREBP-1, accumulation of cellular TG, and
secretion of apoB. HepG2SOCS3 shows lower phosphorylation levels
of IRS-1 Tyr896 and Akt Ser473 in response to insulin. Finally, insulin
stimulation produced an additive effect with SOCS3 overexpression,
further inducing PCSK9, SREBP-1, FAS and apoB mRNA. In
conclusion, our data candidate PCSK9 as a gene involved in lipid
metabolism regulated by pro-inflammatory cytokine TNF-α, in a
SOCS3 dependent manner.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
SOCS3; PCSK9; insulin-resistance
Elenco autori:
C. Ricci, M. Ruscica, C. Macchi, P. Magni, R. Cristofani, J. Liu, A. Corsini, N. Ferri
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