TGF-beta1 up-regulates expression of ABCA1, ABCG1 and SR-BI through liver X receptor alpha signaling pathway in THP-1 macrophage-derived foam cells.
OBJECTIVE
High density lipoprotein (HDL) and its apolipoproteins can promote cholesterol efflux from macrophage foam cells via the ATP-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B type I (SR-BI). Liver X receptors (LXRs) operate as cholesterol sensors which may protect from cholesterol overload by stimulating cholesterol efflux from cells to HDL through ABCA1, ABCG1 and SR-BI. The regulation of ABCA1, ABCG1 and SR-BI expression by cytokines present within the microenvironment of the atheroma may play an important role in determining the impact of reverse cholesterol transport on the atherosclerotic lesion. In the current study, we examined the effect of transforming growth factor-beta1 (TGF-beta1) on expressions of ABCA1, ABCG1 and SR-BI and explored the role of LXR alpha in the regulation of ABCA1, ABCG1 and SR-BI in THP-1 macrophage-derived foam cells.


RESULTS
TGF-beta1 significantly increased expressions of ABCA1, ABCG1 and SR-BI at both transcriptional and translational levels in a dose-dependent and time-dependent manner. Cellular cholesterol content was decreased while cholesterol efflux was increased by TGF-beta1 treatment. Moreover, LXR alpha was up-regulated by TGF-beta1 treatment. In addition, LXR alpha small interfering RNA completely abolished the promotion effect induced by TGF-beta1.


CONCLUSIONS
These results provide evidence that TGF-beta1 up-regulates expressions of ABCA1, ABCG1 and SR-BI through the LXR alpha pathway in THP-1 macrophage-derived foam cells.
Hu
Yan-Wei
YW
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan, China.
Wang
Qian
Q
Ma
Xin
X
Li
Xiao-Xu
XX
Liu
Xie-Hong
XH
Xiao
Ji
J
Liao
Duan-Fang
DF
Xiang
Jim
J
Tang
Chao-Ke
CK
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005487:Foam Cells / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D053773:Transforming Growth Factor beta1