IL-13 Augments Histone Demethylase JMJD2B/KDM4B Expression Levels, Activity, and Nuclear Translocation in Airway Fibroblasts in Asthma.
IL-13 Augments Histone Demethylase JMJD2B/KDM4B Expression Levels, Activity, and Nuclear Translocation in Airway Fibroblasts in Asthma.
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DOI：
10.1155/2021/6629844
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发表时间：
2021
影响因子：
4.1
通讯作者：
Hamid Q
中科院分区：
文献类型：
--
作者：
Bajbouj K;Hachim MY;Ramakrishnan RK;Fazel H;Mustafa J;Alzaghari S;Eladl M;Shafarin J;Olivenstein R;Hamid Q
哮喘是世界上最常见的阻塞性肺疾病之一。表观遗传改变，包括DNA甲基化和组蛋白修饰，已报道有助于哮喘发病。由于炎症介质和重塑触发因子IL-13在哮喘的病理生理中发挥核心作用，本研究旨在确定哮喘中可能导致上皮下纤维化的IL-13调节的新表观遗传修饰因子。来自Gene Expression Omnibus （GEO）的公开转录组数据集用于鉴定IL-13暴露后肺成纤维细胞在表观遗传水平上的差异表达基因。分别使用qRT-PCR和western blotting技术，对健康和哮喘个体分离的支气管成纤维细胞在IL-13治疗基线和治疗后所鉴定基因的基因和蛋白表达水平进行评估。用免疫荧光法和免疫组化法分别在支气管成纤维细胞和支气管活检组织中检测其亚细胞定位和组织分布。生物信息学分析显示，在il -13处理的肺成纤维细胞中，组蛋白去甲基化酶JMJD2B/KDM4B的差异表达，这是一种众所周知的表观遗传调节剂，可导致组蛋白上不同赖氨酸残基的去甲基化。哮喘成纤维细胞和支气管活组织检查中JMJD2B的基线表达水平高于健康人。JMJD2B活性也有所增加，其下游靶标H3K36me3的去甲基化证明了这一点。此外，IL-13刺激诱导哮喘成纤维细胞中JMJD2B的表达和H3K36me3的进一步去甲基化。这伴随着JMJD2B进入细胞核的易位增加。这项研究强调了组蛋白去甲基化酶JMJD2B/KDM4B在受IL-13调节的哮喘气道成纤维细胞中的新的病理参与。临床意义。鉴于目前还没有单一的治疗药物可以有效治疗各种亚型的哮喘，本研究为JMJD2B作为一种新的治疗靶点提供了有希望的见解，可能会改善哮喘的治疗和管理。
Asthma is one of the most common obstructive pulmonary diseases worldwide. Epigenetic alterations, including DNA methylation and histone modifications, have been reported to contribute to asthma pathogenesis. Since the inflammation mediator and remodeling trigger, IL-13, is known to play a central role in the pathophysiology of asthma, this study was aimed to identify novel IL-13-regulated epigenetic modifiers in asthma that may contribute to subepithelial fibrosis. Publicly available transcriptomic datasets from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes on an epigenetic level upon IL-13 exposure in lung fibroblasts. Bronchial fibroblasts isolated from healthy and asthmatic individuals were assessed for the gene and protein expression levels of the identified gene at baseline and upon IL-13 treatment using qRT-PCR and western blotting, respectively. Its subcellular localization and tissue distribution were examined in bronchial fibroblasts as well as bronchial biopsies by immunofluorescence and immunohistochemical analysis, respectively. Bioinformatic analysis revealed the differential expression of the histone demethylase JMJD2B/KDM4B, a well-known epigenetic modulator that leads to the demethylation of different lysine residues on histones, in IL-13-treated lung fibroblasts. The baseline expression levels of JMJD2B were higher in asthmatic fibroblasts and in bronchial biopsies in comparison to healthy ones. There was also an increase in JMJD2B activity as evidenced by the demethylation of its downstream target, H3K36me3. Furthermore, IL-13 stimulation induced JMJD2B expression and further demethylation of H3K36me3 in asthmatic fibroblasts. This was accompanied by increased translocation of JMJD2B into the nucleus. This study highlights the novel pathological involvement of the histone demethylase JMJD2B/KDM4B in asthmatic airway fibroblasts that are regulated by IL-13. Clinical implications. Given that there is no single therapeutic medicine to effectively treat the various subtypes of asthma, this study provides promising insights into JMJD2B as a new therapeutic target that could potentially improve the treatment and management of asthma.
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DOI：
10.1183/09031936.00068712
发表时间：
2014-03
期刊：
The European respiratory journal
影响因子：
--
作者：
Firszt R;Francisco D;Church TD;Thomas JM;Ingram JL;Kraft M
通讯作者：
Kraft M
影响因子：
3.7
作者：
Sarna M;Wojcik KA;Hermanowicz P;Wnuk D;Burda K;Sanak M;Czyż J;Michalik M
通讯作者：
Michalik M
DOI：
10.1097/aci.0b013e32835ad0e7
发表时间：
2013-02
影响因子：
2.8
作者：
Karmaus W;Ziyab AH;Everson T;Holloway JW
通讯作者：
Holloway JW
影响因子：
2.8
作者：
Saito, A;Okazaki, H;Takizawa, H
通讯作者：
Takizawa, H
影响因子：
4.3
作者：
Ichikawa, Tomohiro;Panariti, Alice;Hamid, Qutayba
通讯作者：
Hamid, Qutayba