Abstract
Lung tissue plays an important role in the respiratory system of mammals after birth. Early lung development includes six key stages, of which the saccular stage spans the pre- and neonatal periods and prepares the distal lung for alveolarization and gas-exchange. However, little is known about the changes in gene expression between fetal and neonatal lungs. In this study, we performed transcriptomic analysis of messenger RNA (mRNA) and long noncoding RNA (lncRNA) expressed in the lung tissue of fetal and neonatal piglets. A total of 19,310 lncRNAs and 14,579 mRNAs were identified and substantially expressed. Furthermore, 3248 mRNAs were significantly (FDR-adjusted p value ≤ 0.05, FDR: False Discovery Rate) differentially expressed and were mainly enriched in categories related to cell proliferation, immune response, hypoxia response, and mitochondrial activation. For example, CCNA2, an important gene involved in the cell cycle and DNA replication, was upregulated in neonatal lungs. We also identified 452 significantly (FDR-adjusted p value ≤ 0.05) differentially expressed lncRNAs, which might function in cell proliferation, mitochondrial activation, and immune response, similar to the differentially expressed mRNAs. These results suggest that differentially expressed mRNAs and lncRNAs might co-regulate lung development in early postnatal pigs. Notably, the TU64359 lncRNA might promote distal lung development by up-regulating the heparin-binding epidermal growth factor-like (HB-EGF) expression. Our research provides basic lung development datasets and will accelerate clinical researches of newborn lung diseases with pig models.
Highlights
Lung tissue plays a vital role in gas-exchange and is one of the most important parts of the respiratory system for mammalians [1,2,3]
We found that the long noncoding RNA (lncRNA) TU64359 might promote distal lung development by up-regulating the expression of heparin-binding epidermal growth factor-like expression (HB-EGF), which is critical for normal lung development and has a suppressive function that synergistically contributes to decelerating hypercellularity in the distal lung with transforming growth factor-α (TGFα) through epidermal growth factor receptor (EGFR) in perinatal distal lung development [25]
Our study revealed significant morphological differences between the lungs of fetal and neonatal pigs
Summary
Lung tissue plays a vital role in gas-exchange and is one of the most important parts of the respiratory system for mammalians [1,2,3]. The six critically important stages of normal lung development are: organogenesis, pseudoglandular, canalicular, saccular, alveolization, and microvascular maturation [4,5,6]. The saccular stage, often defined in gestational weeks 24–36 and can even last until the fourth to fifth year in human postnatal life, is critical for normal lung development because it prepares the distal lung for subsequent alveolarization and gas-exchange after birth, Genes 2018, 9, 443; doi:10.3390/genes9090443 www.mdpi.com/journal/genes. The lung is liquid-filled [8,9,10] and takes no part in gas-exchange because of high pulmonary vascular resistance and immature respiratory function [11,12]. It is necessary for the lung to be sufficiently developed at birth to perform the function of gas-exchange, which requires numerous physiological changes to occur [14].
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