Sine oculis homeobox homolog 1 plays a critical role in pulmonary fibrosis.
Sine oculis homeobox homolog 1 plays a critical role in pulmonary fibrosis.
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DOI：
10.1172/jci.insight.142984
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发表时间：
2022-05-23
期刊：
影响因子：
8
通讯作者：
Karmouty-Quintana, Harry
中科院分区：
文献类型：
--
作者：
Wilson, Cory;Mertens, Tinne C. J.;Shivshankar, Pooja;Bi, Weizen;Collum, Scott D.;Wareing, Nancy;Ko, Junsuk;Weng, Tingting;Naikawadi, Ram P.;Wolters, Paul J.;Maire, Pascal;Jyothula, Soma S. K.;Thandavarayan, Rajarajan A.;Ren, Dewei;Elrod, Nathan D.;Wagner, Eric J.;Huang, Howard J.;Dickey, Burton F.;Ford, Heide L.;Karmouty-Quintana, Harry
特发性肺纤维化（IPF）是一种治疗选择有限的致死性疾病。发育转录因子Sine oculis同源框同系物1（SIX 1）在肺纤维化病理生理学中的作用尚不清楚。IPF肺组织样本和IPF衍生的肺泡II型细胞（AT 2）显示SIX 1 mRNA和蛋白水平显著增加，SIX 1转录辅激活因子EYA 1和EYA 2升高。Six 1在博莱霉素处理的小鼠和AT 2细胞中端粒重复序列结合因子1（Trf 1）缺失导致的自发性肺纤维化模型中也上调。AT 2细胞中Six 1的条件性缺失预防或停止了BLM诱导的肺纤维化，如通过纤维化的组织学负担的显著减少、纤维化介质表达的减少和肺功能的改善所测量的。这些作用与BLM诱导的纤维化中SIX 1过表达后体内肺上皮细胞中巨噬细胞迁移抑制因子（MIF）增加有关。MIF启动子驱动的荧光素酶试验证明Six 1与MIF启动子的5′-TCAGG-3′共有序列直接结合，确定了SIX 1驱动的MIF表达在肺纤维化发病机制中的可能机制，并为IPF治疗中的靶向提供了潜在的新途径。
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. The role of the developmental transcription factor Sine oculis homeobox homolog 1 (SIX1) in the pathophysiology of lung fibrosis is not known. IPF lung tissue samples and IPF-derived alveolar type II cells (AT2) showed a significant increase in SIX1 mRNA and protein levels, and the SIX1 transcriptional coactivators EYA1 and EYA2 were elevated. Six1 was also upregulated in bleomycin-treated (BLM-treated) mice and in a model of spontaneous lung fibrosis driven by deletion of Telomeric Repeat Binding Factor 1 (Trf1) in AT2 cells. Conditional deletion of Six1 in AT2 cells prevented or halted BLM-induced lung fibrosis, as measured by a significant reduction in histological burden of fibrosis, reduced fibrotic mediator expression, and improved lung function. These effects were associated with increased macrophage migration inhibitory factor (MIF) in lung epithelial cells in vivo following SIX1 overexpression in BLM-induced fibrosis. A MIF promoter–driven luciferase assay demonstrated direct binding of Six1 to the 5′-TCAGG-3′ consensus sequence of the MIF promoter, identifying a likely mechanism of SIX1-driven MIF expression in the pathogenesis of lung fibrosis and providing a potentially novel pathway for targeting in IPF therapy.
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影响因子：
11.8
作者：
Ahmed, Mohi;Wong, Elaine Y. M.;Sun, Jianbo;Xu, Jinshu;Wang, Feng;Xu, Pin-Xian
通讯作者：
Xu, Pin-Xian
影响因子：
7.3
作者：
Collum, Scott D.;Chen, Ning-Yuan;Karmouty-Quintana, Harry
通讯作者：
Karmouty-Quintana, Harry
影响因子：
5.7
作者：
Chen, Pei-Fen;Luo, Ya-ling;Al-Abed, Yousef
通讯作者：
Al-Abed, Yousef
DOI：
10.1165/rcmb.2013-0310oc
发表时间：
2015-02-01
影响因子：
6.4
作者：
Bauer, Yasmina;Tedrow, John;Kaminski, Naftali
通讯作者：
Kaminski, Naftali
影响因子：
9.1
作者：
Das, Rituparna;Moss, Jeremy E.;Bucala, Richard
通讯作者：
Bucala, Richard