StayCurrentMD · Dysregulation of CITED2 in abnormal lung development in the nitrofen rat model
Article1 min read·Published Jan 2024Older

Dysregulation of CITED2 in abnormal lung development in the nitrofen rat model

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Article · Jan 2024 · 1 min read

In brief

In brief

This study investigates CITED2 gene expression patterns during abnormal lung development in a rat model of congenital diaphragmatic hernia (CDH). Researchers found stage-specific dysregulation of CITED2, with reduced expression at E18 and increased expression at E21, suggesting this transcription factor plays a critical role in the pulmonary hypoplasia associated with CDH.

Written by the GCMD Library team from the article.

Abstract

Purpose

CITED2 both modulates lung, heart and diaphragm development. The role of CITED2 in the pathogenesis of congenital diaphragmatic hernia (CDH) is unknown. We aimed to study CITED2 during abnormal lung development in the nitrofen model.

Methods

Timed-pregnant rats were given nitrofen on embryonic day (E) 9 to induce CDH. Fetal lungs were harvested on E15, 18 and 21. We performed RT-qPCR, RNAscope™ in situ hybridization and immunofluorescence staining for CITED2.

Results

We observed no difference in RT-qPCR (control: 1.09 ± 0.22 and nitrofen: 0.95 ± 0.18, p = 0.64) and in situ hybridization (1.03 ± 0.03; 1.04 ± 0.03, p = 0.97) for CITED2 expression in E15 nitrofen and control pups. At E18, CITED2 expression was reduced in in situ hybridization of nitrofen lungs (1.47 ± 0.05; 1.14 ± 0.07, p = 0.0006), but not altered in RT-qPCR (1.04 ± 0.16; 0.81 ± 0.13, p = 0.33). In E21 nitrofen lungs, CITED2 RNA expression was increased in RT-qPCR (1.04 ± 0.11; 1.52 ± 0.17, p = 0.03) and in situ hybridization (1.08 ± 0.07, 1.29 ± 0.04, p = 0.02). CITED2 protein abundance was higher in immunofluorescence staining of E21 nitrofen lungs (2.96 × 109 ± 0.13 × 109; 4.82 × 109 ± 0.25 × 109, p < 0.0001).

Conclusion

Our data suggest that dysregulation of CITED2 contributes to abnormal lung development of CDH, as demonstrated by the distinct spatial–temporal distribution in nitrofen-induced lungs.

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