Reduction of inorganic phosphate-induced human smooth muscle cells calcification by inhibition of protein kinase A and p38 mitogen-activated protein kinase
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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.
KeywordsSmooth muscle cell Calcification Protein kinase A Mitogen-activated protein kinase Alkaline phosphatase
This work was financially supported by a grant-in-aid for Scientific Research (B) (KAKENHI Grant Number 23310085) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.
- 7.Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R, Schinke T, Karsenty G, Giachelli CM (2001) Smooth muscle cell phenotype transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res 89:1147–1154PubMedCrossRefGoogle Scholar
- 12.Prosdocimo DA, Wyler SC, Romani AM, O’Neill WC, Dubyak GR (2010) Regulation of vascular smooth muscle cell calcification by extracellular pyrophosphate homeostasis: synergistic modulation by cyclic AMP and hyperphosphatemia. Am J Physiol Cell Physiol 298:C702–C713PubMedCrossRefPubMedCentralGoogle Scholar