IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis.
IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis.
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DOI：
10.1186/s12931-022-02241-0
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发表时间：
2022-11-15
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
--
作者：
与特发性肺纤维化(IPF)相关的肺动脉高压(PH)预示着不良预后。IL-11与纤维化疾病有关，但它们在肺血管中的作用尚不清楚。在此，我们分析了IL-11在IPF患者PH中的作用及其可能机制。以正常对照组(n = 2 0)、肺间质纤维化(n = 2 0)和肺间质纤维化相关肺高压(n = 2 0)为研究对象，研究IL-11和IL-11Rα的表达和定位。在Tie2-GFP转基因小鼠上建立IL-11和博莱霉素诱导的肺纤维化与PH相关的两种模型，以评价IL-11和内皮细胞在肺动脉重塑中的作用。分析IL-11和可溶性IL-11Rα对人肺动脉内皮细胞及血管内皮细胞转化和增殖的影响。IL-11和IL-11Rα在肺间质纤维化伴肺间质纤维化组和非肺间质性肺间质纤维化组的肺动脉和血清中均有高表达。重组小鼠(RM)IL-11诱导Tie2-GFP小鼠肺纤维化和肺高压，体内激活EnMT作为肺动脉重塑和肺纤维化的贡献者。瞬时转导siRNA-IL-11可减轻Tie2-GFP博莱霉素肺纤维化和肺高压。人(H)-rIL-11和可溶性hrIL-11Rα在体外可诱导内皮细胞向间充质转化、肺动脉平滑肌细胞向成肌成纤维细胞样转化、细胞增殖和衰老。IL-11和IL-11Rα在特发性肺纤维化患者的肺动脉高表达，参与了肺血管重塑和肺高压的发生。网上版载有补充材料，可在10.1186/s12931-022-02241-0查阅。
Pulmonary hypertension (PH) associated to idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. IL-11 has been implicated in fibrotic diseases, but their role on pulmonary vessels is unknown. Here we analyzed the contribution of IL-11 to PH in patients with IPF and the potential mechanism implicated. Pulmonary arteries, lung tissue and serum of control subjects (n = 20), IPF (n = 20) and PH associated to IPF (n = 20) were used to study the expression and localization of IL-11 and IL-11Rα. Two models of IL-11 and bleomycin-induced lung fibrosis associated to PH were used in Tie2-GFP transgenic mice to evaluate the contribution of IL-11 and endothelial cells to pulmonary artery remodeling. The effect of IL-11 and soluble IL-11Rα on human pulmonary artery endothelial cells and smooth muscle cell transformations and proliferation were analyzed. IL-11 and IL-11Rα were over-expressed in pulmonary arteries and serum of patients with PH associated to IPF vs IPF patients without PH. Recombinant mice (rm)IL-11 induced lung fibrosis and PH in Tie2-GFP mice, activating in vivo EnMT as a contributor of pulmonary artery remodeling and lung fibrosis. Transient transfection of siRNA-IL-11 reduced lung fibrosis and PH in Tie2-GFP bleomycin model. Human (h)rIL-11 and soluble hrIL-11Rα induced endothelial to mesenchymal transition (EnMT) and pulmonary artery smooth muscle cell to myofibroblast-like transformation, cell proliferation and senescence in vitro. IL-11 and IL-11Rα are overexpressed in pulmonary arteries of PH associated to IPF patients, and contributes to pulmonary artery remodeling and PH. The online version contains supplementary material available at 10.1186/s12931-022-02241-0.
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影响因子：
82.9
作者：
Lagares D;Ghassemi-Kakroodi P;Tremblay C;Santos A;Probst CK;Franklin A;Santos DM;Grasberger P;Ahluwalia N;Montesi SB;Shea BS;Black KE;Knipe R;Blati M;Baron M;Wu B;Fahmi H;Gandhi R;Pardo A;Selman M;Wu J;Pelletier JP;Martel-Pelletier J;Tager AM;Kapoor M
通讯作者：
Kapoor M
影响因子：
3.3
作者：
Blanco, Isabel;Ribas, Jesus;Barbera, Joan A.
通讯作者：
Barbera, Joan A.
影响因子：
4.6
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
通讯作者：
Cook SA
DOI：
10.1016/j.str.2007.02.006
发表时间：
2007-04
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Matadeen R;Hon WC;Heath JK;Jones EY;Fuller S
通讯作者：
Fuller S
影响因子：
9.6
作者：
Lettieri, CJ;Nathan, SD;Shorr, AF
通讯作者：
Shorr, AF