Long non-coding RNA MALAT1 targeting STING transcription promotes bronchopulmonary dysplasia through regulation of CREB.
Long non-coding RNA MALAT1 targeting STING transcription promotes bronchopulmonary dysplasia through regulation of CREB.
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DOI：
10.1111/jcmm.15661
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Zhou GP
中科院分区：
文献类型：
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作者：
Chen JH;Feng DD;Chen YF;Yang CX;Juan CX;Cao Q;Chen X;Liu S;Zhou GP
支气管肺发育不良（BPD）是早产儿的一种严重并发症，其特征是肺泡化和炎症增加。过早暴露于高氧被认为是BPD发病机制的关键因素。尚未研制出有效的预防或治疗药物。干扰素基因刺激因子（Stimulator of interferon gene，STING）与多种肺部疾病的炎症和细胞凋亡有关。据报道，长非编码RNA MALAT 1参与BPD。然而，MALAT 1如何调节STING表达仍然未知。在这项研究中，我们评估了STING和MALAT 1在BPD新生儿、高氧大鼠模型和肺上皮细胞系的肺组织中上调。然后，使用流式细胞术和细胞增殖实验，我们发现STING或MALAT 1的下调抑制了高氧处理的细胞的凋亡，并促进了细胞的增殖。随后，qRT-PCR、蛋白质印迹和双荧光素酶报告基因测定显示，抑制MALAT 1降低了STING的表达和启动子活性。此外，转录因子CREB通过染色质免疫沉淀显示其在STING转录中的调节作用。总之，MALAT 1与CREB相互作用以调节BPD新生儿中的STING转录。STING、CREB和MALAT 1可能是预防和治疗BPD的有效靶点。
Bronchopulmonary dysplasia (BPD) is a severe complication of preterm infants characterized by increased alveolarization and inflammation. Premature exposure to hyperoxia is believed to be a key contributor to the pathogenesis of BPD. No effective preventive or therapeutic agents have been created. Stimulator of interferon gene (STING) is associated with inflammation and apoptosis in various lung diseases. Long non‐coding RNA MALAT1 has been reported to be involved in BPD. However, how MALAT1 regulates STING expression remains unknown. In this study, we assessed that STING and MALAT1 were up‐regulated in the lung tissue from BPD neonates, hyperoxia‐based rat models and lung epithelial cell lines. Then, using the flow cytometry and cell proliferation assay, we found that down‐regulating of STING or MALAT1 inhibited the apoptosis and promoted the proliferation of hyperoxia‐treated cells. Subsequently, qRT‐PCR, Western blotting and dual‐luciferase reporter assays showed that suppressing MALAT1 decreased the expression and promoter activity of STING. Moreover, transcription factor CREB showed its regulatory role in the transcription of STING via a chromatin immunoprecipitation. In conclusion, MALAT1 interacts with CREB to regulate STING transcription in BPD neonates. STING, CREB and MALAT1 may be promising therapeutic targets in the prevention and treatment of BPD.
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影响因子：
28.2
作者：
Della Corte CM;Byers LA
通讯作者：
Byers LA
检查点控制蛋白在高氧中的双相反应：暴露于较低水平的氧气会诱导实验性狒狒BPD中的基因组维持基因。
影响因子：
4.3
作者：
Das KC;Wasnick JD
通讯作者：
Wasnick JD
影响因子：
11
作者：
Bartolotti N;Bennett DA;Lazarov O
通讯作者：
Lazarov O
CREBZF 作为 STAT3 通路的关键调节剂控制小鼠肝脏再生
影响因子：
13.5
作者：
Hu, Zhimin;Han, Yamei;Li, Yu
通讯作者：
Li, Yu
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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