Angiotensin II induces EMMPRIN expression in THP-1 macrophages via the NF-kappaB pathway.
BACKGROUND
Recent studies on atherosclerosis showed that an inducer of MMPs, EMMPRIN, is highly expressed in human atheromas. This suggested the important role of EMMPRIN in the stability of atherosclerotic plaques. Angiotensin II, one of the main functional peptides in the renin-angiotensin system, is involved in the advancement of atherosclerosis. We evaluated the effect of angiotensin II on EMMPRIN expression in THP-1 macrophages, and postulated the potential mechanisms underlying its effects.


RESULTS
We established THP-1 macrophages using PMA. The effect of angII on EMMPRIN expression in THP-1 macrophages was then investigated. Results from analyses of RT-PCR and western blotting showed that angII could upregulate EMMPRIN expression. This was mediated via the AT1R, but not the AT2R. The NF-kappaB inhibitor PDTC and P65 RNAi treatment could suppress the effect of angII on EMMPRIN, suggesting the involvement of the NF-kappaB pathway. A gelatin zymography assay showed that MMP-9 activity was related to EMMPRIN expression.


CONCLUSIONS
AngII upregulates the expression of EMMPRIN. NF-kappaB is the critical factor involved in the upregulation of EMMPRIN induced by angII.
Yang
Li-xia
LX
Department of Cardiology, Kunming General Hospital of Chengdu Military Area, Yunnan 650032, China. doctorlxyang@163.com
Liu
Hong
H
Guo
Rui-wei
RW
Ye
Jinshan
J
Wang
Xian-mei
XM
Qi
Feng
F
Guo
Chuan-ming
CM
Liang
Xing
X
D000804:Angiotensin II / Q000494:pharmacology*; D051926:Basigin / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
C497886:BSG protein, human; D016328:NF-kappa B; D000804:Angiotensin II; D051926:Basigin; D020780:Matrix Metalloproteinase 9