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Publication : T0901317, an LXR agonist, augments PKA-induced vascular cell calcification.

First Author  Hsu JJ Year  2009
Journal  FEBS Lett Volume  583
Issue  8 Pages  1344-8
PubMed ID  19327357 Mgi Jnum  J:147981
Mgi Id  MGI:3843117 Doi  10.1016/j.febslet.2009.03.039
Citation  Hsu JJ, et al. (2009) T0901317, an LXR agonist, augments PKA-induced vascular cell calcification. FEBS Lett 583(8):1344-8
abstractText  We examined the effect of liver X receptor (LXR) agonists on vascular calcification, prevalent in atherosclerotic lesions. T0901317, an LXR agonist, augmented protein kinase A (PKA)-induced mineralization and alkaline phosphatase (ALP) activity in aortic smooth muscle cells isolated from wild-type, but not from Lxrbeta(-/-)mice. A six-hour T0901317 treatment augmented the PKA-induced expression of the phosphate transporter Pit-1, a positive regulator of mineralization, suggesting a direct role. A ten-day T0901317 treatment attenuated PKA-induced expression of mineralization inhibitors, osteopontin and ectonucleotide pyrophosphatase/phosphodiesterase-1, suggesting an indirect role. The effects of T0901317 were attenuated by inhibition of ALP, Pit-1 and Rho-associated kinase, but not by inhibition of PKA. These results suggest that T0901317-augmented mineralization occurs downstream of PKA, involving both direct and indirect LXR-mediated pathways.
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