Pediatr Surg Int

. 2020 Oct 13. doi: 10.1007/s00383-020-04757-2. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/33048239/

miR-200 family expression during normal and abnormal lung development due to congenital diaphragmatic hernia at the later embryonic stage in the nitrofen rat model

Drew Mulhall ^1 2 3, Naghmeh Khoshgoo ^1 2 3, Robin Visser ^1 2 3, Barbara Iwasiow ^1 2 3, Chelsea Day ^1 2 3, Fuqin Zhu ^1 2 3, Patrice Eastwood ⁴, Richard Keijzer ^5 6 7 8Affiliations expand

• PMID: 33048239
• DOI: 10.1007/s00383-020-04757-2

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Abstract

Introduction: Congenital diaphragmatic hernia (CDH) is a life-threatening disease associated with pulmonary hypoplasia. CDH occurs approximately 1 in every 2000-3000 live births, and the pathophysiology is unknown. MicroRNAs are short, non-coding RNAs that control gene expression through post-transcriptional regulation. Based on our previous work, we hypothesized that the miR-200 family is differentially expressed in normal and abnormal lung development. We aimed to examine the expression of the miR-200 family during normal and hypoplastic lung development due to CDH.

Methods: We performed reverse transcriptase polymerase chain reaction (RT-qPCR) and fluorescent in situ hybridization (FISH) to study the expression levels and distribution of the miR-200 family members on embryonic day 21 (E21) rat control and nitrofen-induced hypoplastic CDH lungs.

Results: RT-qPCR showed up-regulation of miR-200a in hypoplastic CDH lungs. FISH showed contrasting expression patterns for miR- 200a, miR-200c, and miR-429 between control and hypoplastic CDH lungs, while we could not detect miR-141 in control and hypoplastic CDH lungs.

Conclusion: We demonstrate a specific expression pattern of miR-200 family members in hypoplastic CDH lungs different from control lungs. This study suggests that disruption of miR-200 family expression plays a role in the pathogenesis of pulmonary hypoplasia associated with CDH.

Keywords: CDH; Developmental biology; Epigenetics; Genetics; Lung development; microRNA.