Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
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DOI：
10.1038/srep33666
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发表时间：
2016-09-20
影响因子：
4.6
通讯作者：
Ohshima M
中科院分区：
文献类型：
--
作者：
Horie M;Yamaguchi Y;Saito A;Nagase T;Lizio M;Itoh M;Kawaji H;Lassmann T;Carninci P;Forrest AR;Hayashizaki Y;Suzutani T;Kappert K;Micke P;Ohshima M
牙周炎影响着一半以上的成年人，是一个重大的公共卫生问题。先前，我们从牙周炎患者中分离出一组牙龈成纤维细胞（GFs），称为牙周炎相关成纤维细胞（PAFs），它们具有高度的胶原降解能力。为了阐明它们的分子特征，我们利用CAGE-seq对健康和牙周炎感染牙龈组织中分离的GFs进行了分析，并与FANTOM5图谱相结合。与来自其他器官部位的成纤维细胞相比，来自健康牙龈组织的GFs显示出独特的CAGE谱模式，其特征是特异性表达发育重要的转录因子，如BARX1、PAX9、LHX8和DLX5。此外，还发现了一种与LHX8相关的新型长链非编码RNA。此外，我们发现DLX5调节RUNX2转录物长变体的表达，该变体在GFs中特别活跃，而在牙周炎影响的对应体中则不活跃。在GFs中敲低这些因子导致细胞外基质（ECM）成分的表达改变。这些结果表明，DLX5和RUNX2通过其远端启动子激活是GFs的一个独特特征，并且对ECM调控很重要。paf中这些转录因子的下调可能与它们降解胶原的特性有关，这可能影响牙周炎的过程。
Periodontitis is affecting over half of the adult population, and represents a major public health problem. Previously, we isolated a subset of gingival fibroblasts (GFs) from periodontitis patients, designated as periodontitis-associated fibroblasts (PAFs), which were highly capable of collagen degradation. To elucidate their molecular profiles, GFs isolated form healthy and periodontitis-affected gingival tissues were analyzed by CAGE-seq and integrated with the FANTOM5 atlas. GFs from healthy gingival tissues displayed distinctive patterns of CAGE profiles as compared to fibroblasts from other organ sites and characterized by specific expression of developmentally important transcription factors such as BARX1, PAX9, LHX8, and DLX5. In addition, a novel long non-coding RNA associated with LHX8 was described. Furthermore, we identified DLX5 regulating expression of the long variant of RUNX2 transcript, which was specifically active in GFs but not in their periodontitis-affected counterparts. Knockdown of these factors in GFs resulted in altered expression of extracellular matrix (ECM) components. These results indicate activation of DLX5 and RUNX2 via its distal promoter represents a unique feature of GFs, and is important for ECM regulation. Down-regulation of these transcription factors in PAFs could be associated with their property to degrade collagen, which may impact on the process of periodontitis.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
3.8
作者：
Horie M;Saito A;Noguchi S;Yamaguchi Y;Ohshima M;Morishita Y;Suzuki HI;Kohyama T;Nagase T
通讯作者：
Nagase T
影响因子：
30.8
作者：
Kizawa, H;Kou, I;Ikegawa, S
通讯作者：
Ikegawa, S
影响因子：
7.6
作者：
Ohshima, M.;Yamaguchi, Y.;Kappert, K.
通讯作者：
Kappert, K.
影响因子：
3.3
作者：
Kou, Ikuyo;Nakajima, Masahiro;Ikegawa, Shiro
通讯作者：
Ikegawa, Shiro