Effects and molecular mechanisms of intrauterine infection/inflammation on lung development.
Abstract | BACKGROUND: METHODS: An animal model of intrauterine infection/ inflammation was established with pregnant SD rats endocervically inoculated with E.coli. The fetal and neonatal rats were observed at embryonic day (E) 17, 19, 21 and postnatal day (P) 1, 3, 7, 14, respectively. Body weight, lung weight, the expression levels of NLRP3, TNF-α, IL-lβ, IL-6, VEGF, Collagen I, SP-A, SP-B and SP-C in the lung tissues of fetal and neonatal rats were measured. Expression profiles of 1218 kinds of miRNAs in the lungs of neonatal rats were detected by miRNA microarray technique. Target genes of the identified miRNAs were predicted through online software. RESULTS: Intrauterine infection/ inflammation compromised not only weight development but also lung development of the fetal and neonatal rats. The results showed significantly increased expression of NLRP3, TNF-α, IL-1β, IL-6, Collagen I, and significantly decreased expression of VEGF, SP-A, SP-B and SP-C in the fetal and neonatal rat lung tissues in intrauterine infection group compared to the control group at different observation time point (P < 0.05). Forty-three miRNAs with significant differential expression were identified. Possible target genes regulated by the identified miRNAs are very rich. CONCLUSIONS: Intrauterine infection/ inflammation results in lung histological changes which are very similar to those observed in BPD. Possible mechanisms may include NLRP3 inflammasome activation followed by inflammatory cytokines expression up-regulated, inhibiting the expression of pulmonary surfactant proteins, interfering with lung interstitial development. There are many identified miRNAs which target a wide range of genes and may play an important role in the processes of lung injury and BPD.
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Authors | Jiarong Pan, Canyang Zhan, Tianming Yuan, Weiyan Wang, Ying Shen, Yi Sun, Tai Wu, Weizhong Gu, Lihua Chen, Huimin Yu |
Journal | Respiratory research
(Respir Res)
Vol. 19
Issue 1
Pg. 93
(05 10 2018)
ISSN: 1465-993X [Electronic] England |
PMID | 29747649
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Animals, Newborn
- Body Weight
(physiology)
- Female
- Inflammation
(metabolism, pathology)
- Inflammation Mediators
(metabolism)
- Lung
(growth & development, metabolism, pathology)
- Organ Size
(physiology)
- Pregnancy
- Pregnancy Complications, Infectious
(metabolism, pathology)
- Rats
- Rats, Sprague-Dawley
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