The Role of Macrophage Migration Inhibitory Factor (MIF) in Asthmatic Airway Remodeling.
The Role of Macrophage Migration Inhibitory Factor (MIF) in Asthmatic Airway Remodeling.
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巨噬细胞迁移抑制因子 (MIF) 在哮喘气道重塑中的作用。
DOI：
10.4168/aair.2021.13.1.88
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Mo B
中科院分区：
文献类型：
--
作者：
Li R;Wang F;Wei J;Lin Y;Tang G;Rao L;Ma L;Xu Q;Wu J;Lv Q;Zhou R;Lei H;Zhao X;Yao D;Xiao B;Huang H;Zhang J;Mo B
近年来的研究表明，巨噬细胞移动抑制因子（MIF）在哮喘炎症反应中起重要作用。MIF在调节气道重塑中的作用至今尚未完全阐明。本研究假设MIF通过增强气道平滑肌细胞（ASMC）自噬促进气道重塑，并探讨其具体机制。通过将腺相关病毒（AAV）载体（MIF突变体AAV 9）注入小鼠肺组织中，进行C57 BL/6小鼠肺组织中的MIF敲低。自噬标记物ATG 5（ATG 5 +/−）遗传缺陷的小鼠用于检测自噬在卵清蛋白（OVA）-哮喘小鼠模型中的作用。此外，在体外模型中，采用抑制剂、抗体和慢病毒转染技术来阻断MIF和CD 74的表达。首先，小鼠肺组织中的MIF敲低显示在OVA小鼠模型中显著减少的气道重塑。其次，在OVA攻击模型中，ASMC自噬增加。自噬标记物ATG 5（ATG 5 +/−）遗传缺陷的小鼠经OVA致敏和激发后，其气道重塑比遗传野生型哮喘小鼠低。MIF在体外可诱导ASMC自噬。MIF促进ASMC自噬的细胞来源是巨噬细胞。最后，MIF以CD 74依赖的方式促进ASMC自噬。MIF可能通过增强ASMC自噬作用而促进哮喘气道重塑。巨噬细胞源性MIF可通过靶向CD 74促进ASMC自噬。
Recent studies have demonstrated that macrophage migration inhibitory factor (MIF) is of importance in asthmatic inflammation. The role of MIF in modulating airway remodeling has not yet been thoroughly elucidated to date. In the present study, we hypothesized that MIF promoted airway remodeling by intensifying airway smooth muscle cell (ASMC) autophagy and explored the specific mechanisms. MIF knockdown in the lung tissues of C57BL/6 mice was conducted by instilling intratracheally adeno-associated virus (AAV) vectors (MIF-mutant AAV9) into mouse lung tissues. Mice genetically deficient in the autophagy marker ATG5 (ATG5+/−) was used to detect the role of autophagy in ovalbumin (OVA)-asthmatic murine models. Moreover, to block the expression of MIF and CD74 in vitro models, inhibitors, antibodies and lentivirus transfection techniques were employed. First, MIF knockdown in the lung tissues of mice showed markedly reduced airway remodeling in OVA murine mice models. Secondly, ASMC autophagy was increased in the OVA-challenged models. Mice genetically deficient in the autophagy marker ATG5 (ATG5+/−) that were primed and challenged with OVA showed lower airway remodeling than genetically wild-type asthmatic mice. Thirdly, MIF can induce ASMC autophagy in vitro. Moreover, the cellular source of MIF which promoted ASMC autophagy was macrophages. Finally, MIF promoted ASMC autophagy in a CD74-dependent manner. MIF can increase asthmatic airway remodeling by enhancing ASMC autophagy. Macrophage-derived MIF can promote ASMC autophagy by targeting CD74.
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影响因子：
5.7
作者：
Chen, Pei-Fen;Luo, Ya-ling;Al-Abed, Yousef
通讯作者：
Al-Abed, Yousef
影响因子：
15.9
作者：
Benigni, F;Atsumi, T;Bucala, R
通讯作者：
Bucala, R
巨噬细胞是巨噬细胞迁移抑制因子的重要且以前未被认可的来源。
影响因子：
15.3
作者：
Calandra, Thierry;Bernhagen, Juergen;Mitchell, Robert A.;Bucala, Richard
通讯作者：
Bucala, Richard
影响因子：
4.4
作者：
Meyer-Siegler, Katherine L.;Iczkowski, Kenneth A.;Vera, Pedro L.
通讯作者：
Vera, Pedro L.
DOI：
10.1165/rcmb.2018-0169oc
发表时间：
2019-05-01
影响因子：
6.4
作者：
McAlinden, Kielan D.;Deshpande, Deepak A.;Sharma, Pawan
通讯作者：
Sharma, Pawan