Multidrug resistance-associated protein 4 regulates cAMP-dependent signaling pathways and controls human and rat SMC proliferation
J. Clin. Invest. Yassine Sassi, et al. 118:2747 doi:10.1172/JCI35067 [
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Figure 2Upregulation of MRP4 in vitro and in vivo in proliferating SMCs. (
A) MRP4 mRNA level quantified by quantitative real-time PCR in cultured hCASMCs exposed for 72 h to 5% or 0.1% S normalized to the value obtained in 0.1% S. (***
P < 0.001;
n = 3) (
B) Western blot analysis of MRP4 protein expression in the same conditions as described in
A. PP2B (calcineurin) was used as a loading control and cyclin D1 as a marker of proliferation. (
C) MRP4 protein level normalized to PP2B (**
P < 0.01). (
D) Representative sections of non-injured or balloon-injured rat carotid arteries 14 d after injury. Immunostaining revealed MRP4 expression in the media (m) and predominantly in the neointima (ni). Expression of MRP4 correlated with that of NM-B, a phenotypic marker of SMC proliferation. Scale bars: 50 μm.
