Mir-21 Mediates the Inhibitory Effect of Ang (1-7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts.
Mir-21 Mediates the Inhibitory Effect of Ang (1-7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts.
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Mir-21 通过靶向肺成纤维细胞中的 Spry1 介导 Ang (1-7) 对 AngII 诱导的 NLRP3 炎症小体激活的抑制作用
DOI：
10.1038/s41598-017-13305-3
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发表时间：
2017-10-30
影响因子：
4.6
通讯作者：
Meng Y
中科院分区：
文献类型：
--
作者：
Sun NN;Yu CH;Pan MX;Zhang Y;Zheng BJ;Yang QJ;Zheng ZM;Meng Y
由血管紧张素II（AngII）诱导的microRNA-21（mir-21）在肺纤维化的发展中起重要作用，并且已知NLRP 3炎性体参与纤维化发生。然而，在肺纤维化中mir-21和NLRP 3炎性小体之间是否存在联系尚不清楚。血管紧张素转换酶2/血管紧张素（1-7）[ACE 2/Ang（1-7）]已被证明可减轻AngII诱导的肺纤维化，但尚不清楚ACE 2/Ang（1-7）是否通过抑制AngII诱导的mir-21表达来保护肺纤维化。本研究的目的是研究mir-21是否激活NLRP 3炎性体并介导AngII和ACE 2/Ang（1-7）对肺成纤维细胞凋亡和胶原合成的不同作用。在体内，AngII加剧博莱霉素（BLM）诱导的大鼠肺纤维化，并升高mir-21和NLRP 3炎性小体。相反，ACE 2/Ang（1-7）减轻BLM诱导的肺纤维化，并减少mir-21和NLRP 3炎性体。在体外，AngII通过上调mir-21激活NLRP 3炎性体，ACE 2/Ang（1-7）通过下调AngII诱导的mir-21抑制NLRP 3炎性体激活。过表达mir-21可通过ERK/NF-κB通路激活NLRP 3炎性小体，导致肺成纤维细胞抗凋亡和胶原合成。这些结果表明，mir-21通过靶向肺成纤维细胞中的Spry 1介导ACE 2/Ang（1-7）对AngII诱导的NLRP 3炎性体活化的抑制作用。
MicroRNA-21 (mir-21) induced by angiotensin II (AngII) plays a vital role in the development of pulmonary fibrosis, and the NLRP3 inflammasome is known to be involved in fibrogenesis. However, whether there is a link between mir-21 and the NLRP3 inflammasome in pulmonary fibrosis is unknown. Angiotensin-converting enzyme 2/angiotensin(1–7) [ACE2/Ang(1–7)] has been shown to attenuate AngII-induced pulmonary fibrosis, but it is not clear whether ACE2/Ang(1–7) protects against pulmonary fibrosis by inhibiting AngII-induced mir-21 expression. This study’s aim was to investigate whether mir-21 activates the NLRP3 inflammasome and mediates the different effects of AngII and ACE2/Ang(1–7) on lung fibroblast apoptosis and collagen synthesis. In vivo, AngII exacerbated bleomycin (BLM)-induced lung fibrosis in rats, and elevated mir-21 and the NLRP3 inflammasome. In contrast, ACE2/Ang(1–7) attenuated BLM-induced lung fibrosis, and decreased mir-21 and the NLRP3 inflammasome. In vitro, AngII activated the NLRP3 inflammasome by up-regulating mir-21, and ACE2/Ang(1–7) inhibited NLRP3 inflammasome activation by down-regulating AngII-induced mir-21. Over-expression of mir-21 activated the NLRP3 inflammasome via the ERK/NF-κB pathway by targeting Spry1, resulting in apoptosis resistance and collagen synthesis in lung fibroblasts. These results indicate that mir-21 mediates the inhibitory effect of ACE2/Ang(1–7) on AngII-induced activation of the NLRP3 inflammasome by targeting Spry1 in lung fibroblasts.
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影响因子：
4.3
作者：
Li, Si;Liang, Zhu;Zou, Fangdong
通讯作者：
Zou, Fangdong
影响因子：
3.2
作者：
Liu, Xiujuan;Hong, Quan;Xu, Lihong
通讯作者：
Xu, Lihong
DOI：
10.4049/jimmunol.0903937
发表时间：
2010-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
He X;Mekasha S;Mavrogiorgos N;Fitzgerald KA;Lien E;Ingalls RR
通讯作者：
Ingalls RR
雷公藤红素诱导的 MiR-21/ERK 信号通路抑制可减轻心脏纤维化和功能障碍
影响因子：
--
作者：
Cheng, Mian;Wu, Gang;Zhang, Cuntai
通讯作者：
Zhang, Cuntai
影响因子：
4.6
作者：
Liu Y;Li Y;Li N;Teng W;Wang M;Zhang Y;Xiao Z
通讯作者：
Xiao Z