MicroRNA-421 inhibition alleviates bronchopulmonary dysplasia in a mouse model via targeting Fgf10.

Abstract

Bronchopulmonary dysplasia (BPD) is a common and refractory disease affecting newborn children and infants with alveolar dysplasia and declined pulmonary function. Several microRNAs (miRNAs) have been found to be differentially expressed in BPD progression. This study further explores the role of miR-421 via fibroblast growth factor 10 (Fgf10) in mice with BPD. A mouse model of BPD was established through the induction of hyperoxia, in which the expression pattern of miR-421 and Fgf10 was identified. Furthermore, adenovirus-packed vectors were injected in mice to intervene miR-421 and Fgf10 expression, including miR-421 mimics or inhibitors, and si-Fgf10 to explore the role of miR-421 and Fgf10 in BPD. The target relationship between miR-421 and Fgf10 was investigated. Inflammatory response and cell apoptosis were observed in the mice, with inflammatory cytokines and apoptosis-related factors detected by applying Reverse transcription quantitative polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Fgf10 was confirmed as a target gene of miR-421. Elevated expression of miR-421 was evident, while Fgf10 was poorly expressed in BPD. upregulation of miR-421 and silence of Fgf10 aggravated inflammatory response in lung tissue and promoted lung cell apoptosis in BPD. The aforementioned alterations could be reversed by downregulation of miR-421. Collectively, inhibition of miR-421 can assist in the development of BPD in mice BPD by upregulating Fgf10. Therefore, the present study provides a probable target for the treatment of BPD.