Association of the proliferation of lung fibroblasts with the ERK1/2 signaling pathway in neonatal rats with hyperoxia-induced lung fibrosis
Association of the proliferation of lung fibroblasts with the ERK1/2 signaling pathway in neonatal rats with hyperoxia-induced lung fibrosis
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DOI：
10.3892/etm.2018.6999
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发表时间：
2019-01-01
影响因子：
2.7
通讯作者：
Xue, Xindong
中科院分区：
文献类型：
--
作者：
Hu, Yu;Fu, Jianhua;Xue, Xindong
支气管肺发育不良（BPD）是早产儿常见的严重并发症。虽然临床特征和病理改变已被很好地描述，但肺泡发育不良和间质纤维化的发病机制尚不清楚。肺成纤维细胞（LF）存在于细胞外基质中，在肺上皮损伤和BPD纤维化发展中起重要作用。本研究探讨了高氧诱导的体外原代肝纤维化细胞增殖及其可能的机制。新生大鼠暴露于90%的氧气，而对照组大鼠保持在正常的气氛中。在出生后第3、7和14天分离原发LF。高氧通过加速细胞周期从G1期到S期的进展诱导在第7天和第14天分离的LF的增殖。与对照组相比，高氧组第7天和第14天I型胶原蛋白分泌和mRNA表达增加。与室内空气对照组相比，高氧显著增加了细胞外信号调节激酶（ERK）的磷酸化，并显著增加了I型胶原的表达。研究结果表明，LF增殖反应的增加高氧与ERK 1/2磷酸化。这种机制可能有助于LF的过度增殖，导致正常肺泡的形成受到干扰。
Bronchopulmonary dysplasia (BPD) is a common, serious complication occurring in premature infants. Although clinical characteristics and pathologic changes are well described, the pathogenesis of alveolar dysplasia and interstitial fibrosis is less clear. Lung fibroblasts (LFs) are present in the extracellular matrix and serve essential roles during pulmonary epithelial injury and in response to fibrosis development in BPD. The current study investigated hyperoxia-induced proliferation of primary LFs in vitro and mechanisms that may be involved. Newborn rats were exposed to 90% oxygen, while control rats were kept in normal atmosphere. Primary LFs were isolated on postnatal day 3, 7 and 14. Hyperoxia-induced proliferation of LFs isolated on day 7 and 14 by accelerating the cell cycle progression from G1 to S phase. Collagen type I protein secretion and mRNA expression on day 7 and 14 were increased by hyperoxia compared with the controls. Hyperoxia significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK) and significantly increased collagen type I expression compared with the room air control group. The findings indicated that an increase in LF proliferation in response to hyperoxia was associated with ERK1/2 phosphorylation. This mechanism may contribute to over-proliferation of LFs leading to disturbed formation of normal alveoli.