Inhibition of phosphodiesterase-5 suppresses calcineurin/NFAT- mediated TRPC6 expression in pulmonary artery smooth muscle cells.
Inhibition of phosphodiesterase-5 suppresses calcineurin/NFAT- mediated TRPC6 expression in pulmonary artery smooth muscle cells.
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抑制磷酸二酯酶 5 可抑制肺动脉平滑肌细胞中钙调神经磷酸酶/NFAT 介导的 TRPC6 表达
DOI：
10.1038/s41598-017-06350-5
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发表时间：
2017-07-20
影响因子：
4.6
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Li S;Pan Y;Ke R;Xie X;Zhai C;Shi W;Wang J;Yan X;Chai L;Wang Q;Zhang Q;Su X;Yang L;Gao L;Li M
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus. Further study indicated that inhibition of calcineurin by cyclosporine A or knockdown of NFATc4 using small interfering RNA suppressed ET-1-induced TRPC6 up-regulation. In addition, luciferase reporter assay showed that NFATc4 directly regulated the expression of TRPC6 in PASMCs. Inhibition of PDE5 by sildenafil suppressed ET-1-induced activation of calcineurin/NFATc4 signaling pathway and consequent TRPC6 up-regulation in PASMCs, while these inhibitory effects of sildenafil were abolished by PKG inhibitor Rp-8Br-cGMPs. Taken together, our study indicates that ET-1 stimulates TRPC6 expression by activation of calcineurin/NFATc4 signaling pathway, and inhibition of PDE5 suppresses calcineurin/NFATc4- mediated TRPC6 expression in PASMCs in a cGMP-PKG-dependent manner.
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DOI：
10.1007/978-3-319-26974-0_10
发表时间：
2016-01-01
期刊：
CALCIUM ENTRY PATHWAYS IN NON-EXCITABLE CELLS
影响因子：
--
作者：
Bouron, Alexandre;Chauvet, Sylvain;Rosado, Juan A.
通讯作者：
Rosado, Juan A.
西地那非抑制大鼠肺动脉平滑肌中典型瞬时受体电位表达的慢性缺氧上调
影响因子：
5.5
作者：
Lu, Wenju;Ran, Pixin;Wang, Jian
通讯作者：
Wang, Jian
DOI：
10.1164/rccm.200312-1668oc
发表时间：
2004-11-15
影响因子：
24.7
作者：
Kunichika, N;Landsberg, JW;Yuan, JXJ
通讯作者：
Yuan, JXJ
影响因子：
6.2
作者：
Serrano-Perez, Maria C.;Fernandez, Miriam;Tranque, Pedro
通讯作者：
Tranque, Pedro
影响因子：
24
作者：
Humbert, M;Morrell, NW;Rabinovitch, M
通讯作者：
Rabinovitch, M