Interleukin-11 is important for vascular smooth muscle phenotypic switching and aortic inflammation, fibrosis and remodeling in mouse models.
Interleukin-11 is important for vascular smooth muscle phenotypic switching and aortic inflammation, fibrosis and remodeling in mouse models.
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DOI：
10.1038/s41598-020-74944-7
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发表时间：
2020-10-20
影响因子：
4.6
通讯作者：
Cook SA
中科院分区：
文献类型：
--
作者：
Lim WW;Corden B;Ng B;Vanezis K;D'Agostino G;Widjaja AA;Song WH;Xie C;Su L;Kwek XY;Tee NGZ;Dong J;Ko NSJ;Wang M;Pua CJ;Jamal MH;Soh B;Viswanathan S;Schafer S;Cook SA
转化生长因子β-1（TGFβ1）是血管平滑肌细胞（VSMC）表型转换的主要驱动因素，是动脉疾病的重要病理生物学。我们对TGFβ1刺激的人主动脉或动脉VSMCs进行了RNA测序，结果显示白细胞介素11（IL 11）大量且一致的上调。IL 11在VSMC中具有未知的功能，VSMC高度表达IL 11受体α，提示自分泌环。在体外，IL 11激活ERK信号，但抑制STAT 3活性，并导致VSMC表型转换的程度与TGFβ1或血管紧张素II（ANGII）刺激相似。IL 11信号的遗传或治疗抑制减少了TGFβ1或ANGII诱导的VSMC表型转换，使IL 11活性位于这些因子的下游。Myh 11驱动的IL 11表达的小鼠的主动脉被重塑，收缩性降低，但基质和炎症基因表达增加。在两种动脉压力负荷模型中，IL 11在主动脉中上调，中和IL 11抗体沿着基质和促炎基因表达减少重塑。这些数据表明IL 11在VSMC表型转换、血管炎症和主动脉病理学中起重要作用。
Transforming growth factor beta-1 (TGFβ1) is a major driver of vascular smooth muscle cell (VSMC) phenotypic switching, an important pathobiology in arterial disease. We performed RNA-sequencing of TGFβ1-stimulated human aortic or arterial VSMCs which revealed large and consistent upregulation of Interleukin 11 (IL11). IL11 has an unknown function in VSMCs, which highly express the IL11 receptor alpha, suggestive of an autocrine loop. In vitro, IL11 activated ERK signaling, but inhibited STAT3 activity, and caused VSMC phenotypic switching to a similar extent as TGFβ1 or angiotensin II (ANGII) stimulation. Genetic or therapeutic inhibition of IL11 signaling reduced TGFβ1- or ANGII-induced VSMC phenotypic switching, placing IL11 activity downstream of these factors. Aortas of mice with Myh11-driven IL11 expression were remodeled and had reduced contractile but increased matrix and inflammatory genes expression. In two models of arterial pressure loading, IL11 was upregulated in the aorta and neutralizing IL11 antibodies reduced remodeling along with matrix and pro-inflammatory gene expression. These data show that IL11 plays an important role in VSMC phenotype switching, vascular inflammation and aortic pathobiology.
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DOI：
10.1042/cs20090372
发表时间：
2010-03-09
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Daugherty A;Rateri DL;Charo IF;Owens AP;Howatt DA;Cassis LA
通讯作者：
Cassis LA
DOI：
10.1126/science.1192149
发表时间：
2011-04-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Holm TM;Habashi JP;Doyle JJ;Bedja D;Chen Y;van Erp C;Lindsay ME;Kim D;Schoenhoff F;Cohn RD;Loeys BL;Thomas CJ;Patnaik S;Marugan JJ;Judge DP;Dietz HC
通讯作者：
Dietz HC
影响因子：
15.9
作者：
Elia, Leonardo;Kunderfranco, Paolo;Quintavalle, Manuela
通讯作者：
Quintavalle, Manuela
小鼠横向主动脉收缩后主动脉重塑被AT1受体阻断减弱。
DOI：
10.1161/atvbaha.113.301624
发表时间：
2013-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Kuang SQ;Geng L;Prakash SK;Cao JM;Guo S;Villamizar C;Kwartler CS;Peters AM;Brasier AR;Milewicz DM
通讯作者：
Milewicz DM
影响因子：
8.7
作者：
Ford, CM;Li, SH;Pickering, JG
通讯作者：
Pickering, JG