S1P induces pulmonary artery smooth muscle cell proliferation by activating calcineurin/NFAT/OPN signaling pathway
S1P induces pulmonary artery smooth muscle cell proliferation by activating calcineurin/NFAT/OPN signaling pathway
复制标题
S1P通过激活钙调神经磷酸酶/NFAT/OPN信号通路诱导肺动脉平滑肌细胞增殖
DOI：
10.1016/j.bbrc.2019.06.160
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发表时间：
2019
影响因子：
3.1
通讯作者：
Li Manxiang
中科院分区：
文献类型：
--
作者：
Yan Xin;Wang Jian;Zhu Yanting;Feng Wei;Zhai Cui;Liu Lu;Shi Wenhua;Wang Qingting;Zhang Qianqian;Chai Limin;Li Manxiang
The upregulation of osteopontin(OPN) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells(PASMCs), and activation of PPARγ has been shown to suppress OPN expression in THP-1 cells. However, the molecular mechanisms underlying the upregulation of OPN expression and PPARγ agonist modulation of OPN expression in PASMCs remain largely unclear. Here we found that S1P stimulated PASMCs proliferation and up-regulated OPN expression in rat PASMCs, which was accompanied with the activation of phospholipase C(PLC), calcineurin and translocation of NFATc3 to nucleus. Further study showed that inhibition of PLC by U73122, suppression of calcineurin activity by cyclosporine A(CsA) or knockdown of NFATc3 using small interfering RNA suppressed S1P-induced OPN up-regulation. Activation of PPARγ by pioglitazone suppressed S1P-induced activation of calcineurin/NFATc3 signaling pathway and followed OPN up-regulation. Taken together, our study indicates that S1P stimulates OPN expression by activation of PLC/calcineurin/NFATc3 signaling pathway, and activation of PPARγ suppresses calcineurin/NFATc3-mediated OPN expression in PASMCs.
