Association of the proliferation of lung fibroblasts with the ERK1/2 signaling pathway in neonatal rats with hyperoxia‑induced lung fibrosis

Hu,Yu; Fu,Jianhua; Xue,Xindong

doi:10.3892/etm.2018.6999

Association of the proliferation of lung fibroblasts with the ERK1/2 signaling pathway in neonatal rats with hyperoxia‑induced lung fibrosis

Authors:
- Yu Hu
- Jianhua Fu
- Xindong Xue
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Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: November 21, 2018 https://doi.org/10.3892/etm.2018.6999
Pages: 701-708
Copyright : © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

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.

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