Suppression of Discoidin Domain Receptor 1 by RNA Interference Attenuates Lung Inflammation1
Suppression of Discoidin Domain Receptor 1 by RNA Interference Attenuates Lung Inflammation1
复制标题
通过 RNA 干扰抑制盘状蛋白结构域受体 1 可减轻肺部炎症1
作者：
W. Matsuyama;Masaki Watanabe;Yuko Shirahama;R. Hirano;H. Mitsuyama;I. Higashimoto;M. Osame;K. Arimura
盘状结构域受体1（DDR1）是一种受体酪氨酸激酶，其配体是胶原。最近，我们报道了DDR1在体外人类白细胞的细胞因子产生和特发性肺纤维化中的体内表达中的关联。然而，其在体内炎症中的作用尚未完全阐明。小干扰RNA（siRNA）可以诱导特异性抑制体内外基因表达。在这项研究中，使用博莱霉素诱导的肺纤维化小鼠模型，我们给予siRNA对DDR1 transnasally和评估肺组织学变化，细胞因子表达和信号分子激活。在组织学上，针对DDR1的siRNA成功地降低了体内DDR1表达并减弱了博来霉素诱导的炎性细胞浸润。此外，它还能显著降低支气管肺泡灌洗液中的炎性细胞计数和细胞因子如MCP-1、MIP-1 α和MIP-2的浓度。随后，博莱霉素诱导的支气管肺泡灌洗液中TGF-β的上调被显著抑制，肺中胶原沉积减少。此外，针对DDR1的SiRNA显着抑制博莱霉素诱导的肺部P38 MAPK激活。综合考虑，我们认为DDR1有助于博来霉素诱导的肺部炎症和纤维化的发展。
Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase whose ligand is collagen. Recently, we have reported the association of DDR1 in the cytokine production of human leukocytes in in vitro and in vivo expression in idiopathic pulmonary fibrosis. However, its role in in vivo inflammation has not been fully elucidated. Small interference RNA (siRNA) can induce specific suppression of in vitro and in vivo gene expression. In this study, using a bleomycin-induced pulmonary fibrosis mouse model, we administered siRNA against DDR1 transnasally and evaluated histological changes, cytokine expression, and signaling molecule activation in the lungs. Histologically, siRNA against DDR1 successfully reduced in vivo DDR1 expression and attenuated bleomycin-induced infiltration of inflammatory cells. Furthermore, it significantly reduced inflammatory cell counts and concentrations of cytokines such as MCP-1, MIP-1α, and MIP-2 in bronchoalveolar lavage fluid. Subsequently, bleomycin-induced up-regulation of TGF-β in bronchoalveolar lavage fluid was significantly inhibited, and collagen deposition in the lungs was reduced. Furthermore, siRNA against DDR1 significantly inhibited bleomycin-induced P38 MAPK activation in the lungs. Considered together, we propose that DDR1 contributes to the development of bleomycin-induced pulmonary inflammation and fibrosis.
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DOI：
--
发表时间：
2000
期刊：
--
影响因子：
--
作者：
J. Nick;S. Young;Kevin Brown;N. Avdi;P. Arndt;B. Suratt;M. Janes;P. Henson;G. Worthen
通讯作者：
J. Nick;S. Young;Kevin Brown;N. Avdi;P. Arndt;B. Suratt;M. Janes;P. Henson;G. Worthen
基质金属蛋白酶降解巢蛋白。
DOI：
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发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sires,UI;Griffin,GL;Broekelmann,TJ;Mecham,RP;Murphy,G;Chung,AE;Welgus,HG;Senior,RM
通讯作者：
Senior,RM
影响因子：
4.4
作者：
M. Keane;J. Belperio;T. Moore;B. Moore;D. Arenberg;Robert E. Smith;M. Burdick;S. Kunkel;R. Strieter
通讯作者：
M. Keane;J. Belperio;T. Moore;B. Moore;D. Arenberg;Robert E. Smith;M. Burdick;S. Kunkel;R. Strieter
影响因子：
6
作者：
Ferri, N;Carragher, NO;Raines, EW
通讯作者：
Raines, EW
DOI：
--
发表时间：
2005-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
J. Dejmek;K. Leandersson;J. Manjer;A. Bjartell;S. Emdin;W. Vogel;G. Landberg;T. Andersson
通讯作者：
J. Dejmek;K. Leandersson;J. Manjer;A. Bjartell;S. Emdin;W. Vogel;G. Landberg;T. Andersson