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Letters in Drug Design & Discovery

Author(s): Haiyan Zhu, Chantong Wu, Tianping Bao, Zhaofang Tian*, Huaiping Cheng, Huifang Wang, Wei Wang and Yafei Zheng

DOI: 10.2174/1570180819666220530144117

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Gm15886-Hipk1 Signaling Pathway Plays Important Roles in the Pathogenesis of Bronchopulmonary Dysplasia Mice

Page: [1812 - 1820] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in the respiratory system of premature infants. Gm15886, as a lncRNA, is highly expressed in lung tissue of BPD newborn mice.

Aims: This study aimed to clarify the roles of the Gm15886 gene in the pathogenesis of BPD mice by determining the expression of Gm15886 and Hipk1 in lung tissues.

Methods: Sequence and localization of the Gm15886 gene and the related information of its adjacent genes were obtained using the UCSC browsing tool. The targeting gene of the Gm15886 was predicted using the Ensemble database and double luciferase assay. Neonatal C57BL/6J mice were exposed to 95% hyperoxia for 7 days to generate the hyperoxia-induced BPD mouse model. RT-PCR assay was used to detect Gm15886, Hipk1, and VEGF gene transcriptions in lung tissues in the development process of BPD (0, 3, 5, and 7 days). The pathological changes in lung tissues and Hipk1/VEGF gene transcription in lung tissues were detected in the Gm15886 gene silenced BPD mice.

Results: Gm15886 gene transcription in lung tissues was significantly increased in mice of the hyperoxia model group compared to that in the air control group (p<0.05). Gm15886 gene could completely bind and interact with the base sequence within the second exon of the Hipk1 gene. Hipk1 was a targeting gene for Gm15886. Gene transcription and expression of Hipk1 were remarkably enhanced in mice of the hyperoxia model group compared to that in the air control group (p<0.05). The silencing of the Gm15886 gene improved alveolar morphology and markedly downregulated Hipk1 and upregulated VEGF gene transcription compared to those in the Blank vector BPD group (p<0.05).

Conclusion: Gm15886-Hipk1 signaling pathway plays a critical role in the pathogenesis of BPD through modulating Hipk1 and VEGF gene transcription. This study might provide a theoretical basis for the treatment of BPD.

Keywords: bronchopulmonary dysplasia (BPD), long non-coding RNA, Gm15886, bioinformatics analysis, Hipk1

Graphical Abstract

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