Kang Jeong-Hun, Toita Riki, Asai Daisuke, Yamaoka Tetsuji, Murata Masaharu
Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan,
Heart Vessels. 2014 Sep;29(5):718-22. doi: 10.1007/s00380-013-0427-x. Epub 2013 Oct 19.
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.
高水平的血清磷酸盐与人类平滑肌细胞（HSMC）的钙化有关。我们研究了抑制蛋白激酶A（PKA）和丝裂原活化蛋白激酶（MAPK）信号通路[p38、细胞外信号调节激酶（ERK）和c-Jun氨基末端激酶（JNK）]是否能减少无机磷酸盐（Pi）诱导的HSMC钙化。用抑制剂或小干扰RNA（siRNA）抑制PKA或p38 MAPK可降低高Pi处理的HSMC中的钙水平和碱性磷酸酶活性，但抑制ERK1/2和JNK则无显著变化。此外，添加siRNA和三种抑制剂（PKA、p38和MEK1/2）后细胞活力无显著变化，但JNK抑制剂略微降低了细胞活力。这些结果表明，PKA和p38 MAPK参与了Pi诱导的HSMC钙化，可能是减少血管钙化的良好靶点。
