A murine model of acute lung injury identifies growth factors to promote tissue repair and their biomarkers. (18th December 2018)

• Record Type: Journal Article
• Authors: Kurosawa, Takeyuki; Miyoshi, Shion; Yamazaki, Soh; Nishina, Takashi; Mikami, Tetuo; Oikawa, Akira; Homma, Sakae; Nakano, Hiroyasu
• Is Part Of: Genes to cells. Volume 24:Number 2(2019)
• Page Start: 112
• Page End: 125
• Publication Date: 2018-12-18
• Subjects: apoptosis -- biomarker -- bronchiolar epithelial cell -- Diphtheria toxin receptor -- growth factors -- interleukin 11 -- lung injury -- tissue repair -- type II alveolar epithelial cell (AEC); Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12659
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: Type II alveolar epithelial cells (AEC2s) play a crucial role in the regeneration of type I AECs after acute lung injury. The mechanisms underlying the regeneration of AEC2s are not fully understood. To address this issue, here, we investigated a murine model of acute lung injury using mice expressing human Diphtheria Toxin Receptor (DTR) under the control of Lysozyme M promoter ( LysM‐DTR) . DT injection induced the depletion of AEC2s, alveolar macrophages, and bone marrow (BM)‐derived myeloid cells in LysM‐DTR mice, and the mice died within 6 days after DT injection. Apoptotic AEC2s and bronchiolar epithelial cells appeared at 24 hr, whereas Ki67‐positive proliferating cells appeared in the alveoli and bronchioles in the lung of LysM‐DTR mice at 72–96 hr after DT injection. Transfer of wild‐type BM cells into LysM‐DTR mice accelerated the regeneration of AEC2s along with the up‐regulation of several growth factors. Moreover, several metabolites were significantly decreased in the sera of LysM‐DTR mice compared with WT mice after DT injection, suggesting that these metabolites might be biomarkers to predict AEC2s injury. Together, LysM‐DTR mice might be useful to identify growth factors to promote lung repair and the metabolites to predict the severity of lung injury. Abstract : Diphtheria toxin injection induced severe lung injury in LysM‐DTR mice. Transfer of wild‐type BM cells into LysM‐DTR mice accelerated the regeneration of AEC2s along with the up‐regulation of several growth factors. Several metabolites were significantly decreased in the sera of LysM‐DTR mice compared with WT mice after DT injection, suggesting that these metabolites might be biomarkers to predict AEC2s injury.