Abstract
Background Bronchopulmonary dysplasia (BPD) is a common and serious complication in premature infants. Lung fibroblasts (LFs) are present in the extracellular matrix and participate in pulmonary development in response to BPD. The aim of this study was to investigate the effect of extracellular signal-regulated kinase (ERK) on LFs cultured from newborn rats. Material and Methods. Primary LFs were isolated and treated with epidermal growth factor (EGF, 20 ng/mL) in the presence or absence of an ERK inhibitor, PD98059 (10 μmol/L). Phosphorylated ERK1/2 (p-ERK1/2) protein levels were determined using immunocytochemistry, western blotting, and real-time reverse transcription quantitative (RT–q)PCR. LF proliferation was examined by flow cytometry and a cell counting kit-8 assay. LF transdifferentiation was examined by protein and mRNA expression of α-smooth muscle actin (α-SMA) by immunocytochemistry, western blotting, and RT–qPCR. LF migration was examined by the transwell method. Results Phosphorylated ERK1/2, which was activated by EGF, promoted LF proliferation by accelerating cell-cycle progression from the G1 to S phase. After treatment with PD98059, the expression of p-ERK1/2 in LFs, cellular proliferation, and the percentage of cells in S phase were significantly decreased. Phosphorylated ERK1/2 also promoted the differentiation of LFs into myofibroblasts through increased α-SMA synthesis and migration. Conclusion The activation of ERK promotes proliferation, transdifferentiation, and migration of lung fibroblasts from newborn rats.
Highlights
Bronchopulmonary dysplasia (BPD) is a serious chronic pulmonary complication often seen in preterm neonates experiencing long-term ventilation support or oxygen exposure [1]
The main manifestation of pulmonary interstitial fibrosis is the uncontrolled growth of lung fibroblasts that are deposited in the pulmonary interstitium or displaced normal lung epithelium [9]
We have previously found that hyperoxia promoted ERK1/2 phosphorylation and the proliferation of lung fibroblasts rats in vitro [12]
Summary
Bronchopulmonary dysplasia (BPD) is a serious chronic pulmonary complication often seen in preterm neonates experiencing long-term ventilation support or oxygen exposure [1]. During normal lung development and differentiation, epithelial and mesenchymal cells ordinarily proliferate and interact. The interruption of such processes may impact lung structure and function and cause disastrous consequences [6]. Most studies have focused on alveolar epithelial cells in BPD, lung fibroblasts (LFs) participate in normal lung development and respond to lung injury. Lung fibroblasts (LFs) are present in the extracellular matrix and participate in pulmonary development in response to BPD. Phosphorylated ERK1/2, which was activated by EGF, promoted LF proliferation by accelerating cell-cycle progression from the G1 to S phase. Phosphorylated ERK1/2 promoted the differentiation of LFs into myofibroblasts through increased α-SMA synthesis and migration. The activation of ERK promotes proliferation, transdifferentiation, and migration of lung fibroblasts from newborn rats
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