Deoxycholic acid is involved in the initiation and progression of atherosclerosis.

Abstract

Deoxycholic acid (DCA), a kind of bile acids, is elevated in serum of patients with chronic kidney disease (CKD). The present study examines the influence of DCA on the functions of vascular smooth muscle cells (VSMCs) because CKD is associated with cardiovascular diseases such as atherosclerosis. As a result, DCA induced JNK phosphorylation and migration of VSMCs whereas JNK inhibitor prevented DCA‐induced the migration. In addition, phosphorylation of c‐Jun, a downstream molecule of JNK, was promoted upon stimulation with DCA. On the base of this result, we checked whether DCA promotes the expression level of PDGFRβ that has a c‐Jun binding site in the promoter region. When VSMCs were incubated with DCA for 24 h, the expression level of PDGFRβ was upregulated. Furthermore, increased ERK phosphorylation by incubation with DCA for 24 h correlated with DCA‐induced the expression of PDGFRβ. These results demonstrate that DCA directly influences the functions of VSMCs. Taken together, elevated serum concentration of DCA is involved in the pathogenesis of atherosclerosis in patients with CKD. This work is supported by Regional Innovation Strategy Support Program of the MEXT, The Japanese Government.