A murine model of acute lung injury identifies growth factors to promote tissue repair and their biomarkers.
Genes Cells
; 24(2): 112-125, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30474194
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores
/
Transplante de Medula Óssea
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Lesão Pulmonar Aguda
/
Metaboloma
/
Células Epiteliais Alveolares
/
Fator de Crescimento Semelhante a EGF de Ligação à Heparina
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article