Reduction of inorganic phosphate-induced human smooth muscle cells calcification by inhibition of protein kinase A and p38 mitogen-activated protein kinase

Jeong Hun Kang, Riki Toita, Daisuke Asai, Tetsuji Yamaoka, Masaharu Murata

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    High levels of serum phosphate are associated with calcification of human smooth muscle cells (HSMCs). We investigated whether inhibition of protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) signals [p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK)] can reduce inorganic phosphate (Pi)-induced HSMC calcification. Inhibition of PKA or p38 MAPK by inhibitors or small interfering RNAs (siRNAs) reduced Ca levels and alkaline phosphatase activities in HSMCs treated with high Pi, but inhibition of ERK1/2 and JNK showed no significant changes. Moreover, there were no significant changes in cell viability on adding siRNAs and three inhibitors (PKA, p38, and MEK1/2), but JNK inhibitor slightly reduced cell viability. These results show that PKA and p38 MAPK are involved in the Pi-induced calcification of HSMCs, and may be good targets for reducing vascular calcification.

    Original languageEnglish
    Pages (from-to)718-722
    Number of pages5
    JournalHeart and Vessels
    Volume29
    Issue number5
    DOIs
    Publication statusPublished - Jan 1 2013

    All Science Journal Classification (ASJC) codes

    • Cardiology and Cardiovascular Medicine

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