CIKS (Act1 or TRAF3IP2) mediates Angiotensin-II-induced Interleukin-18 expression, and Nox2-dependent cardiomyocyte hypertrophy.
CIKS (Act1 or TRAF3IP2) mediates Angiotensin-II-induced Interleukin-18 expression, and Nox2-dependent cardiomyocyte hypertrophy.
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DOI：
10.1016/j.yjmcc.2012.04.009
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发表时间：
2012-07
影响因子：
5
通讯作者：
Chandrasekar B
中科院分区：
文献类型：
--
作者：
Valente AJ;Clark RA;Siddesha JM;Siebenlist U;Chandrasekar B
血管紧张素II（Ang-II）的慢性升高可导致心肌炎症、肥大和心力衰竭。在自身免疫性和炎症性疾病中，衔接分子CIKS（与IKK和SAPK/JNK连接）激活IκB激酶/核因子（NF）-κB和JNK/激活蛋白（AP）-1通路。由于Ang-II是NF-κB和AP-1的有效激活剂，我们研究了CIKS是否在Ang-II介导的心肌肥大中起关键作用。在此我们报道了Ang-II诱导CIKS mRNA和蛋白表达，CIKS与IKK和JNK结合可能作为支架蛋白，CIKS依赖性IKK/NF-κB和JNK/AP-1激活，p65和c-Jun磷酸化和核转位，NF-κB和AP-1依赖性IL-18和MMP-9诱导，以及从WT分离的成年心肌细胞肥大，而非CIKS缺失小鼠。这些结果在CIKS敲低后的WT-心肌细胞中被概括。输注Ang-II 7天诱导WT小鼠心脏肥大，胶原含量增加，CIKS mRNA和蛋白表达上调，而CIKS缺失小鼠的心脏肥大和胶原沉积明显减弱，尽管两种类型动物的收缩压和DPI-耐受性超氧化物生成增加相似。此外，Ang-II诱导的IKK/p65和JNK/c-Jun磷酸化、NF-κB和AP-1活化以及IL-18和MMP-9表达在CIKS-null小鼠中也显著减弱。这些结果表明CIKS在Ang-II诱导的心肌细胞肥大和纤维化中是关键的，并且CIKS是Ang-II诱导的氧化还原信号传导中的重要中间体。CIKS是心肌肥厚、纤维化和充血性心力衰竭的潜在治疗靶点。
Chronic elevation of angiotensin (Ang)-II can lead to myocardial inflammation, hypertrophy and cardiac failure. The adaptor molecule CIKS (connection to IKK and SAPK/JNK) activates the IκB kinase/nuclear factor (NF)-κB and JNK/activator protein (AP)-1 pathways in autoimmune and inflammatory diseases. Since Ang-II is a potent activator of NF-κB and AP-1, we investigated whether CIKS is critical in Ang-II-mediated cardiac hypertrophy. Here we report that Ang-II induced CIKS mRNA and protein expression, CIKS binding to IKK and JNK perhaps functioning as a scaffold protein, CIKS-dependent IKK/NF-κB and JNK/AP-1 activation, p65 and c-Jun phosphorylation and nuclear translocation, NF-κB- and AP-1-dependent IL-18 and MMP-9 induction, and hypertrophy of adult cardiomyocytes isolated from WT, but not CIKS-null mice. These results were recapitulated in WT-cardiomyocytes following CIKS knockdown. Infusion of Ang-II for 7 days induced cardiac hypertrophy, increased collagen content, and upregulated CIKS mRNA and protein expression in WT mice, whereas cardiac hypertrophy and collagen deposition were markedly attenuated in the CIKS-null mice, despite a similar increase in systolic blood pressure and DPI-inhibitable superoxide generation in both types of animals. Further, Ang-II-induced IKK/p65 and JNK/c-Jun phosphorylation, NF-κB and AP-1 activation, and IL-18 and MMP-9 expression were also markedly attenuated in CIKS-null mice. These results demonstrate that CIKS is critical in Ang-II-induced cardiomyocyte hypertrophy and fibrosis, and that CIKS is an important intermediate in Ang-II induced redox signaling. CIKS is a potential therapeutic target in cardiac hypertrophy, fibrosis, and congestive heart failure.
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影响因子：
4.4
作者：
Claudio, Estefania;Sonder, Soren Ulrik;Saret, Sun;Carvalho, Gabrielle;Ramalingam, Thirumalai R.;Wynn, Thomas A.;Chariot, Alain;Garcia-Perganeda, Antonio;Leonardi, Antonio;Paun, Andrea;Chen, Amy;Ren, Nina Y.;Wang, Hongshan;Siebenlist, Ulrich
通讯作者：
Siebenlist, Ulrich
影响因子：
32.4
作者：
Kang Z;Altuntas CZ;Gulen MF;Liu C;Giltiay N;Qin H;Liu L;Qian W;Ransohoff RM;Bergmann C;Stohlman S;Tuohy VK;Li X
通讯作者：
Li X
DOI：
10.1073/pnas.160265197
发表时间：
2000-09-12
影响因子：
11.1
作者：
Li, XX;Commane, M;Stark, GR
通讯作者：
Stark, GR
影响因子：
4.8
作者：
Onishi, Reiko M.;Park, Sangmi J.;Gaffen, Sarah L.
通讯作者：
Gaffen, Sarah L.
影响因子：
4.8
作者：
Chandrasekar, B;Mummidi, S;Nemer, M
通讯作者：
Nemer, M