Abstract:Objective: To observe whether CD137 signaling affects the expression of nuclear factor of activated T cells c1(NFATc1) in vascular smooth muscle cells(VSMCs) through CalmodlinCalcineurin(CaMCaN) pathway. Methods: Isolated VSMCs from the mice aortic by explant tissue culture. The experiment was divided into two parts. PartⅠ: the prepared cells were divided into three groups: control group, CD137 activated group, CD137 inhibited group; PartⅡ: control group, CD137 activated group (agonist CD137mAb), siCaM group (siCaM+CD137 activated group), siCaN group (siCaN+CD137 activated group). The levels of CaM, CaN and NFATc1 were evaluated by Western blotting and RTPCR, respectively. Results: (1) The protein and mRNA levels of CaM, CaN and NFATc1 were increased markedly by agitating CD137CD137L signal comparing with control group. When CD137CD137L signaling was restrained by antiCD137 mAb, the protein and mRNA levels of CaM, CaN and NFATc1 were decreased markedly comparing with CD137 activated group. When blocked CaM by CaM siRNA, the protein and mRNA levels of CaM, CaN and NFATc1 were decreased after stimulated by agonist CD137 mAb comparing with CD137 activated group. When blocked CaN, the levels of CaN and NFATc1 were decreased but the level of CaM did not change after stimulated by agonist CD137 mAb comparing with CD137 activated group. Conclusion: CD137CD137L signaling could regulate the expression of NFATc1 through CaMCaN pathway.
[1\]Jung IH, Oh GT. The roles of CD137 signaling in atherosclerosis[J]. Korean Circ J, 2016, 46(6):753-761.\[2\]殷云杰,仲威,严金川.CD137信号及CD137L逆向信号在动脉粥样硬化中作用的研究进展\[J\]. 中华心血管病杂志, 2016, 44(6):557-560.\[3\]Yan J, Yang H, Yuan W, et al. The effect of CD137CD137 ligand interaction on the expression of NFATc1 in apolipoprotein Edeficient mice\[J\]. Int J Cardiol, 2012, 157(1): 134-137.\[4\]陈瑶,严金川,翁嘉懿,等. CD137CD137L信号通路对小鼠动脉粥样斑块及血管平滑肌细胞钙化的影响\[J\]. 中华心血管病杂志,2016,44(10):879-884.\[5\]Torac E, Gaman L, Atanasiu V. The regulator of calcineurin (RCAN1) an important factor involved in atherosclerosis and cardiovascular diseases development\[J\]. J Med Life, 2014, 7(4):481-487.\[6\]Yan J, Yin Y, Zhong W, et al. CD137 regulates NFATc1 expression in mouse VSMCs through TRAF6/NFκB p65 signaling pathway[J]. Mediators Inflamm, 2015, 2015: 639780.\[7\]Li Y, Yan J, Wu C, et al. CD137CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein Edeficient mice\[J\]. PLoS One, 2014, 9(2):e88563.\[8\]殷云杰,严金川,王中群,等. CD137信号通过核因子κB影响小鼠主动脉平滑肌细胞活化T细胞核因子c1表达\[J\].中华心血管病杂志,2015,43(7): 614-618.\[9\]Wei ZF, Tong B, Xia YF, et al. Norisoboldine suppresses osteoclast differentiation through preventing the accumulation of TRAF6TAK1 complexes and activation of MAPKs/NFκB/cFos/NFATc1 Pathways\[J\]. PLoS One, 2013, 8(3):e59171.