IRAK-M Regulates Proliferative and Invasive Phenotypes of Lung Fibroblasts
IRAK-M Regulates Proliferative and Invasive Phenotypes of Lung Fibroblasts
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IRAK-M 调节肺成纤维细胞的增殖和侵袭表型
DOI：
10.1007/s10753-022-01772-4
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发表时间：
2022-12
期刊：
影响因子：
5.1
通讯作者：
Jinming Gao
中科院分区：
文献类型：
--
作者：
Zhoude Zheng;Jia Li;Ye Cui;Wei Wang;Mingqiang Zhang;Youming Zhang;Yan Bai;Sun Ying;Jinming Gao
- 肺成纤维细胞在上皮下纤维化中起重要作用，这是气道重塑的一个特征。IL-1受体相关激酶（IRAK）-M通过调节炎症反应参与气道和肺纤维化的形成。IRAK-M由肺成纤维细胞表达，IRAK-M是否对肺成纤维细胞有直接影响尚不清楚。在本研究中，我们通过沉默或过表达IRAK-M来评估IRAK-M对肺成纤维细胞表型的影响。用屋尘螨（HDM）、IL-33和转化生长因子（TGF）β1刺激小鼠肺成纤维细胞（MLg）。采用小干扰RNA或表达质粒技术沉默或过表达MLg成纤维细胞中的IRAK-M。评价了增殖、迁移、侵袭性和纤维化相关事件。这些刺激导致MLg细胞中IRAK-M表达的显著上调。沉默IRAK-M显著增加肺成纤维细胞的增殖、迁移和侵袭性，而与刺激条件无关。相比之下，IRAK-M过表达显着抑制MLg肺成纤维细胞的增殖和运动。IRAK-M过表达也显著降低MLg细胞中纤连蛋白、I型胶原和α-SMA的表达。在TGFβ1或IL-33刺激下，IRAK-M沉默减少MMP 9的产生，而IRAK-M过表达增加MMP 9的产生。IRAK-M表达的调节影响细胞因子的产生，无论刺激如何，细胞的TNFα和CXCL 10表达均降低或增加。我们的体外数据显示，IRAK-M通过调节肺成纤维细胞的细胞运动性、释放炎性和纤维化细胞因子直接影响肺成纤维细胞。这些可能提示通过调节IRAK-M减缓气道重塑的新靶点。
—Lung fibroblasts play an important role in subepithelial fibrosis, one feature for airway remodeling. IL-1 receptor-associated kinase (IRAK)-M was shown to involve fibrosis formation in airways and lung through regulation of inflammatory responses. IRAK-M is expressed by lung fibroblasts, whether IRAK-M has direct impact on lung fibroblasts remains unclear. In this investigation, we evaluatedin vitroeffect of IRAK-M on phenotypes of lung fibroblasts by silencing or overexpressing IRAK-M. Murine lung fibroblasts (MLg) were stimulated with house dust mite (HDM), IL-33, and transforming growth factor (TGF) β1. Techniques of small interfering RNA or expression plasmid were employed to silence or overexpress IRAK-M in MLg fibroblast cells. Proliferation, migration, invasiveness, and fibrosis-related events were evaluated. Significant upregulation of IRAK-M expression in MLg cells was caused by these stimuli. Silencing IRAK-M significantly increased proliferation, migration, and invasiveness of lung fibroblasts regardless of stimulating conditions. By contrast, IRAK-M overexpression significantly inhibited proliferation and motility of MLg lung fibroblasts. IRAK-M overexpression also significantly decreased the expression of fibronectin, collagen I, and α-SMA in MLg cells. Under stimulation with TGFβ1 or IL-33, IRAK-M silencing reduced MMP9 production, while IRAK-M overexpression increased MMP9 production. Modulation of IRAK-M expression affected cytokines production, either decreased or increased expression of TNFα and CXCL10 by the cells regardless of stimulation. Ourin vitrodata reveal that IRAK-M directly impacts on lung fibroblasts through modulation of cellular motility, release of inflammatory, and fibrotic cytokines of lung fibroblasts. These might suggest a new target by regulation of IRAK-M in slowing airway remodeling.
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由 Toll 样受体复合蛋白的功能模拟引起的过敏性。
影响因子：
64.8
作者：
Trompette, Aurelien;Divanovic, Senad;Visintin, Alberto;Blanchard, Carine;Hegde, Rashmi S.;Madan, Rajat;Thorne, Peter S.;Wills-Karp, Marsha;Gioannini, Theresa L.;Weiss, Jerry P.;Karp, Christopher L.
通讯作者：
Karp, Christopher L.
在屋尘螨诱发的实验性哮喘模型中，IRAK-M 敲除会促进过敏性气道炎症，但不会导致气道高反应性
影响因子：
2.5
作者：
Zhang X;Zhang M;Li L;Chen W;Zhou W;Gao J
通讯作者：
Gao J
DOI：
10.1016/j.jaci.2018.06.008
发表时间：
2019-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Tliba O;Panettieri RA Jr
通讯作者：
Panettieri RA Jr
影响因子：
7.3
作者：
Brilha S;Chong DLW;Khawaja AA;Ong CWM;Guppy NJ;Porter JC;Friedland JS
通讯作者：
Friedland JS
DOI：
10.1016/j.jaci.2011.10.043
发表时间：
2012-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Wu Q;Jiang D;Smith S;Thaikoottathil J;Martin RJ;Bowler RP;Chu HW
通讯作者：
Chu HW