Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling.
Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling.
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DOI：
10.1177/2045893217729096
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发表时间：
2017-10
影响因子：
2.6
通讯作者：
Lawrie A
中科院分区：
文献类型：
--
作者：
Pickworth J;Rothman A;Iremonger J;Casbolt H;Hopkinson K;Hickey PM;Gladson S;Shay S;Morrell NW;Francis SE;West JD;Lawrie A
骨形态发生蛋白受体2（BMPR 2）突变存在于遗传性和特发性肺动脉高压（PAH）患者中。白细胞介素-1（IL-1）的循环水平在患者和动物模型中升高。BMP和IL-1信号之间的相互作用是否可以解释肺动脉高压的局部表现尚不清楚。使用细胞培养、siRNA和从人肺动脉（PASMC）和主动脉（AoSMC）平滑肌细胞分离的RNA的mRNA微阵列分析。R899 X +/-BMPR 2转基因小鼠喂食西方饮食6周，在评估PAH和组织收集之前，每天注射IL-1 β。与AoSMC相比，PASMC对IL-1 β的炎症激活反应降低;然而，BMPR 2降低的PASMC表现出过度反应。用IL-1 β处理的小鼠具有更高的白色血细胞计数和显著升高的IL-6血清蛋白水平和骨保护素（OPG）血浆水平，这与体外数据相一致。表型上，IL-1 β治疗的小鼠表现出肺血管重塑增加。当BMPR 2信号传导减少时，IL-1 β诱导了过度的肺动脉特异性转录组炎症反应。
Bone morphogenetic protein receptor type 2 (BMPR2) mutations are present in patients with heritable and idiopathic pulmonary arterial hypertension (PAH). Circulating levels of interleukin-1 (IL-1) are raised in patients and animal models. Whether interplay between BMP and IL-1 signaling can explain the local manifestation of PAH in the lung remains unclear. Cell culture, siRNA, and mRNA microarray analysis of RNA isolated from human pulmonary artery (PASMC) and aortic (AoSMC) smooth muscle cells were used. R899X+/– BMPR2 transgenic mice fed a Western diet for six weeks were given daily injections of IL-1ß prior to assessment for PAH and tissue collection. PASMC have reduced inflammatory activation in response to IL-1ß compared with AoSMCs; however, PASMC with reduced BMPR2 demonstrated an exaggerated response. Mice treated with IL-1ß had higher white blood cell counts and significantly raised serum protein levels of IL-6 and osteoprotegerin (OPG) plasma levels recapitulating in vitro data. Phenotypically, IL-1ß treated mice demonstrated increased pulmonary vascular remodeling. IL-1ß induces an exaggerated pulmonary artery specific transcriptomic inflammatory response when BMPR2 signaling is reduced.
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影响因子：
15.9
作者：
Rothman, Alexander M. K.;Arnold, Nadine D.;Lawrie, Allan
通讯作者：
Lawrie, Allan
影响因子：
20.1
作者：
Spiekerkoetter E;Guignabert C;de Jesus Perez V;Alastalo TP;Powers JM;Wang L;Lawrie A;Ambartsumian N;Schmidt AM;Berryman M;Ashley RH;Rabinovitch M
通讯作者：
Rabinovitch M
DOI：
10.1111/j.1749-6632.1994.tb39794.x
发表时间：
1994-01-01
期刊：
CELLS AND CYTOKINES IN LUNG INFLAMMATION
影响因子：
--
作者：
VOELKEL, NF;TUDER, R
通讯作者：
TUDER, R
影响因子：
20.1
作者：
Steiner MK;Syrkina OL;Kolliputi N;Mark EJ;Hales CA;Waxman AB
通讯作者：
Waxman AB
DOI：
10.1152/ajplung.00309.2011
发表时间：
2012-03-01
影响因子：
4.9
作者：
Davies, Rachel J.;Holmes, Alan M.;Morrell, Nicholas W.
通讯作者：
Morrell, Nicholas W.