Pediatr Pulmonol. 2020 Apr 1. doi: 10.1002/ppul.24739. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32237270
Overexpression of miR-455-5p affects retinol (vitamin A) absorption by downregulating STRA6 in a nitrofen-induced CDH with lung hypoplasia rat model.
Zheng J1, He Q2, Tang H1, Li J1, Xu H1, Mao X3, Liu G1.
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Abstract
Lung hypoplasia is the main cause of congenital diaphragmatic hernia (CDH)-associated death but pathogenesis remains unclear. MiR-455-5p is involved in lung hypoplasia. We hypothesized that nitrofen causes abnormal miR-455-5p expression during lung development and designed this study to determine the relationship between miR-455-5p, stimulated by retinoic acid 6 (STRA6), and retinol in a nitrofen-induced CDH with lung hypoplasia rat model. Nitrofen or olive oil was administered to Sprague-Dawley rats by gavage on day 9.5 of gestation, and the rats were divided into a nitrofen group and a control group (n = 6). The left lung of fetuses was dissected on day 15.5. The expression of miR-455-5p or STRA6 messenger RNA (mRNA) was determined by quantitative real-time polymerase chain reaction. Average integrated optical density (IOD) of STRA6 protein was determined by immunofluorescence histochemistry. The average retinol level was detected by enzyme-linked immunosorbent assay (n = 6 lungs, respectively). Compared with the control group, the nitrofen group exhibited significantly increased miR-455-5p expression levels (29.450 ± 9.253 vs 5.955 ± 2.330; P = .00045) and significantly decreased STRA6 mRNA levels (0.197 ± 0.097 vs 0.588 ± 0.184; P = .0047). In addition, the average IOD of the STRA6 protein was significantly lower in the nitrofen group (805.643 ± 291.182 vs 1616.391 ± 572.308, P = .015), and the average retinol level was significantly reduced (4.013 ± 0.195 vs 5.317 ± 0.337 µg/L, P = .000). In summary, the overexpression of miR-455-5p affected retinol absorption by downregulating STRA6 in the nitrofen-induced CDH with lung hypoplasia rat model, and this downregulation may be one cause of CDH with lung hypoplasia.
© 2020 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.
KEYWORDS:
STRA6; congenital diaphragmatic hernia; lung hypoplasia; miR-455-5pPMID: 32237270 DOI: 10.1002/ppul.24739
