High expression of Sonic hedgehog in allergic airway epithelia contributes to goblet cell metaplasia.
High expression of Sonic hedgehog in allergic airway epithelia contributes to goblet cell metaplasia.
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Sonic Hedgehog 在过敏性气道上皮细胞中的高表达有助于杯状细胞化生。
DOI：
10.1038/s41385-018-0033-4
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发表时间：
2018-09
影响因子：
8
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Xu C;Zou C;Hussain M;Shi W;Shao Y;Jiang Z;Wu X;Lu M;Wu J;Xie Q;Ke Y;Long F;Tang L;Wu X
Sonic hedgehog（SHH）在胚胎肺中大量表达并且对形态发生至关重要，然而，SHH表达在小鼠中从E17.5开始下降到低得多的水平，并且在人类中从妊娠第21周开始下降。我们发现，SHH的表达在哮喘儿童或过敏性气道疾病小鼠模型的气道上皮细胞中显著上调。具体而言，气道特异性SMO功能丧失显著抑制过敏原诱导的杯状细胞表型，而气道特异性SMO功能获得显著增强过敏性气道疾病小鼠模型中的杯状细胞表型。值得注意的是，用SHH中和抗体或环巴胺的气管内施用强烈地减弱了具有过敏性气道疾病的小鼠模型中的杯状细胞表型。最后，我们确定了编码MUC 5AC粘蛋白的Muc 5AC基因作为GLI转录因子响应SHH的直接靶标，而SAM指向结构域的ETS转录因子和Forkhead box A2，杯状细胞表型的关键转录因子，都作为GLI响应SHH刺激的效应子。总之，过敏性支气管上皮中SHH表达的上调有助于杯状细胞化生;因此，阻断SHH信号传导是慢性气道疾病中上皮重塑的治疗干预的合理方法。
Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs, however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly up-regulated in the airway epithelia of children with asthma or mouse models with allergic airway disease. Specifically, airway-specific SMO loss of function significantly suppresses allergen-induced goblet cell phenotypes, whereas an airway-specific SMO gain of function markedly enhances the goblet cell phenotypes in mouse models with allergic airway disease. Notably, intratracheal administration with SHH- neutralizing antibody or cyclopamine robustly attenuates goblet cell phenotypes in mouse models with allergic airway disease. Finally, we identify that Muc5AC gene encoding MUC5AC mucin serves as a direct target of GLI transcriptional factors in response to SHH, whereas the SAM pointed domain-containing ETS transcription factor and Forkhead box A2, critical transcriptional factors for goblet cell phenotypes, both function as the effectors of GLIs in response to SHH stimulation. Together, the up-regulation of SHH expression in allergic bronchial epithelia contributes to goblet cell metaplasia; thus, blockage of SHH signaling is a rational approach in a therapeutic intervention of epithelial remodeling in chronic airway diseases.
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影响因子：
9.5
作者：
Dunaeva M;Voo S;van Oosterhoud C;Waltenberger J
通讯作者：
Waltenberger J
影响因子：
64.8
作者：
Peng T;Frank DB;Kadzik RS;Morley MP;Rathi KS;Wang T;Zhou S;Cheng L;Lu MM;Morrisey EE
通讯作者：
Morrisey EE
影响因子：
9.2
作者：
Pepicelli, CV;Lewis, PM;McMahon, AP
通讯作者：
McMahon, AP
影响因子：
15.9
作者：
Park, Kwon-Sik;Korfhagen, Thomas R.;Whitsett, Jeffrey A.
通讯作者：
Whitsett, Jeffrey A.
胎盘迷路的正常发育需要通过 Gli2 和 Gli3 的 Sonic Hedgehog
影响因子：
9
作者：
Pan YB;Gong Y;Ruan HF;Pan LY;Wu XK;Tang C;Wang CJ;Zhu HB;Zhang ZM;Tang LF;Zou CC;Wang HB;Wu XM
通讯作者：
Wu XM