Multigenerational Epigenetic Regulation of Allergic Diseases: Utilizing an Experimental Dust Mite-Induced Asthma Model.
Multigenerational Epigenetic Regulation of Allergic Diseases: Utilizing an Experimental Dust Mite-Induced Asthma Model.
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DOI：
10.3389/fgene.2021.624561
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发表时间：
2021
影响因子：
3.7
通讯作者：
Tang WY
中科院分区：
文献类型：
--
作者：
Pulczinski JC;Shang Y;Dao T;Limjunyawong N;Sun Q;Mitzner W;Cheng RY;Tang WY
环境暴露与哮喘风险增加有关，特别是在怀孕和生命早期。在这里，我们使用过敏性肺部疾病的小鼠模型来研究产前和围产期屋尘螨（HDM）过敏原暴露对三代后代表型和转录结果的影响。我们发现，与成年期单独暴露的小鼠相比，母体HDM暴露（F0）与成年期HDM暴露协同作用，导致气道高反应性（AHR）和肺部炎症增强。此外，F1雄性的一个子集在成年期没有被挑战，并被用来产生F2后代，然后被用来产生F3后代。与成年期单独接触HDM的小鼠相比，母系HDM （F0）暴露谱系产生的HDM、F2和F3雄性小鼠在成年后受到HDM攻击时，气道反应性和炎症反应增加。这些发现表明，母体过敏原暴露能够增强过敏性气道疾病的易感性或严重程度。为了研究表观遗传在母体HDM暴露诱导的哮喘易感性中的作用，我们利用全基因组MeDIP-seq和hMeDIP-seq分析鉴定了差异甲基化（DMG）和羟甲基化（DHG）基因，以及它们与AHR增强的关系。此外，我们验证了雄性亚代（F1-F3）中DNA甲基化与dmg和dhg mRNA表达之间的关系。我们发现，与仅在成年期暴露于HDM的F1小鼠相比，在早期和成年期暴露于HDM的F1小鼠中，Kchn1、Nron和Spag17的羟甲基化和上调表达存在差异。与成年期单独暴露的F1小鼠相比，来自母体HDM （F0）暴露谱系的F2和F3中Kcnh1仍然上调。总之，我们证明了母亲在生命早期暴露于HDM可以改变成年HDM暴露后后代的基因表达和表型，导致更严重的疾病。这些影响在最初的侮辱之后至少持续两代，并沿着父系遗传。
Environmental exposures have been linked to increased asthma risk, particularly during pregnancy and in early life. Here we use a mouse model of allergic lung disease to examine the effects of pre- and perinatal house dust mite (HDM) allergen exposure on offspring phenotypic and transcriptional outcomes in three generations. We show that maternal HDM exposure (F0) acts synergistically with adult HDM exposure, leading to enhanced airway hyperresponsiveness (AHR) and lung inflammation when compared to mice exposed solely in adulthood. Additionally, a subset of F1 males were not challenged in adulthood, and used to generate F2 progeny, which was then used to generate F3 progeny. Upon adult challenge to HDM, F2, and F3 males generated from the maternal HDM (F0) exposure lineage displayed increased airway reactivity and inflammation when compared to mice exposed solely in adulthood. These findings indicate that maternal allergen exposure is capable of enhancing either susceptibly to or severity of allergic airway disease. To examine the role of epigenetic inheritance of asthma susceptibility induced by maternal HDM exposure, we utilized a genome-wide MeDIP-seq and hMeDIP-seq analysis to identify genes differentially methylated (DMG) and hydroxymethylated (DHG), and their association with the enhanced AHR. In addition, we validated the relationship between DNA methylation and mRNA expression of the DMGs and DHGs in the male sub-generations (F1-F3). We found the expression of Kchn1, Nron, and Spag17 to be differentially hydroxymethylated and upregulated in the F1 exposed to HDM both in early life and in adulthood when compared to F1 mice exposed solely in adulthood. Kcnh1 remained upregulated in the F2 and F3 from the maternal HDM (F0) exposure lineage, when compared to F1 mice exposed solely in adulthood. In summary, we demonstrated that maternal HDM exposure in early life can alter the gene expression and phenotype of offspring upon adult HDM exposure, resulting in more severe disease. These effects persist at least two generations past the initial insult, transmitted along the paternal line.
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影响因子：
3.7
作者：
Perera, Frederica;Tang, Wan-yee;Herbstman, Julie;Tang, Deliang;Levin, Linda;Miller, Rachel;Ho, Shuk-mei
通讯作者：
Ho, Shuk-mei
影响因子：
168.9
作者：
Celedón, JC;Litonjua, AA;Gold, DR
通讯作者：
Gold, DR
影响因子：
3.8
作者：
Dörmer, P;Spitzer, E;Möller, W
通讯作者：
Möller, W
屋尘螨诱导的气道高反应性中 DNA 甲基化引起的表观遗传改变。
DOI：
10.1165/rcmb.2012-0403oc
发表时间：
2013-08-01
影响因子：
6.4
作者：
Shang, Yan;Das, Sandhya;Tang, Wan-yee
通讯作者：
Tang, Wan-yee
影响因子：
12.4
作者：
Lockett GA;Soto-Ramírez N;Ray MA;Everson TM;Xu CJ;Patil VK;Terry W;Kaushal A;Rezwan FI;Ewart SL;Gehring U;Postma DS;Koppelman GH;Arshad SH;Zhang H;Karmaus W;Holloway JW
通讯作者：
Holloway JW