Research: The RNA-binding protein quaking is upregulated in nitrofen-induced congenital diaphragmatic hernia lungs at the end of gestation

Pediatr Surg Int

. 2024 Mar 13;40(1):78.

 doi: 10.1007/s00383-023-05608-6. https://pubmed.ncbi.nlm.nih.gov/38472353/

The RNA-binding protein quaking is upregulated in nitrofen-induced congenital diaphragmatic hernia lungs at the end of gestation

Yuichiro Miyake 1 2Dustin Ameis 1Wai Hei Tse 1Daywin Patel 1Arzu Ozturk Aptekmann 1Atsuyuki Yamataka 2Richard Keijzer 3

Affiliations expand

Abstract

Background: The RNA-binding protein Quaking (QKI) increases during epithelial-to-mesenchymal transition and its expression is controlled by microRNA-200 family members. Here, we aimed to describe the expression of QKI in the developing lungs of control and nitrofen-induced congenital diaphragmatic hernia lungs (CDH).

Methods: To investigate the expression of QKI, we dissected lungs from control and nitrofen-induced CDH rats on embryonic day 15, 18, 21 (E15, E18, E21). We performed immunofluorescence (IF) and quantitative reverse transcription PCR (RT-qPCR) for QKI expression. Additionally, we assessed Interleukin-6 (IL-6) abundance using IF.

Results: On E21, IF showed that the abundance of all three QKI isoforms and IL-6 protein was higher in CDH lungs compared to control lungs (QKI5: p = 0.023, QKI6: p = 0.006, QKI7: p = 0.014, IL-6: p = 0.045, respectively). Furthermore, RT-qPCR data showed increased expression of QKI5, QKI6, and QKI7 mRNA in E21 nitrofen lungs by 1.63 fold (p = 0.001), 1.63 fold (p = 0.010), and 1.48 fold (p = 0.018), respectively.

Conclusions: Our data show an increase in the abundance and expression of QKI at the end of gestation in nitrofen-induced CDH lungs. Therefore, a disruption in the regulation of QKI during the late stage of pregnancy could be associated with the pathogenesis of abnormal lung development in CDH.

Keywords: Congenital diaphragmatic hernia; Nitrofen rat model; Pulmonary hypoplasia; Quaking; RNA-binding protein.

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