TGF-β inhibits the uptake of modified low density lipoprotein by human macrophages through a Smad-dependent pathway: a dominant role for Smad-2.

ABSTRACT: The anti-atherogenic cytokine, TGF-β, plays a key role during macrophage foam cell formation by modulating the expression of key genes involved in the control of cholesterol homeostasis. Unfortunately, the molecular mechanisms underlying these actions of TGF-β remain poorly understood. In this study we examine the effect of TGF-β on macrophage cholesterol homeostasis and delineate the role of Smads-2 and -3 during this process. Western blot analysis showed that TGF-β induces a rapid phosphorylation-dependent activation of Smad-2 and -3 in THP-1 and primary human monocyte-derived macrophages. Small interfering RNA-mediated knockdown of Smad-2/3 expression showed that the TGF-β-mediated regulation of key genes implicated in the uptake of modified low density lipoproteins and the efflux of ch

SUBMITTER: Michael DR 

PROVIDER: S-EPMC3497875 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature