Gm15886-Hipk1 pathway plays critical roles in pathogenesis of bronchopulmonary dysplasia via modulating Hipk1/VEGF gene transcription in mouse model

Abstract

Background: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in the respiratory system of the premature infants. Gm15886, as a lncRNA, highly expresses in lung tissue of BPD newborn mice. Aims: This study aimed to clarify roles of Gm15886 gene in the pathogenesis of BPD mice, by determining expression of Gm15886 and Hipk1 in lung tissues. Methods: Sequence and localization of Gm15886 gene and the related information of its adjacent genes were obtained using UCSC browsing tool. Targeting gene of Gm15886 gene 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 development process of BPD (0, 3, 5 and 7 days). The pathological changes of 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 hyperoxia model group compared to that in Air control group (P<0.05). Gm15886 gene could completely bind and interact with base sequence, within the second exon of Hipk1 gene. Hipk1 was a targeting gene for Gm15886. Gene transcription and expression of Hipk1 were remarkably enhanced in mice of hyperoxia model group compared with that in Air control group (P<0.05). Silence of Gm15886 gene obviously improved alveolar morphology. Silence of Gm15886 gene markedly downregulated Hipk1 and upregulated VEGF gene transcription compared with those in Blank vector BPD group (P<0.05). Conclusions: 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.