Publications
기타논문
Date: 10 May 2022
Journal: International Journal of Molecular Sciences , Doi: https:// doi.org/10.3390/ijms23105292
2022 | Loss of SP-A in the Lung Exacerbates Pulm<b class="sch_word">on</b>ary Fibrosis…
- Kyunghwa Kim 1 , Dasom Shin 2 , Gaheon Lee 1 and Hyunsu Bae 2,*
첨부파일
Abstract: Idiopathic pulmonary fibrosis (IPF) is a devastating and common chronic lung disease
that is pathologically characterized by the destruction of lung architecture and the accumulation of
extracellular matrix in the lung. Previous studies have shown an association between lung surfactant
protein (SP) and the pathogenesis of IPF, as demonstrated by mutations and the altered expression
of SP in patients with IPF. However, the role of SP in the development of lung fibrosis is poorly
understood. In this study, the role of surfactant protein A (SP-A) was explored in experimental lung
fibrosis induced with a low or high dose of bleomycin (BLM) and CRISPR/Cas9-mediated genetic
deletion of SP-A. Our results showed that lung SP-A deficiency in mice promoted the development
of fibrotic damage and exacerbated inflammatory responses to the BLM challenge. In vitro experiments with murine lung epithelial LA-4 cells demonstrated that in response to transforming growth
factor-β1 (TGF-β1), LA-4 cells had a decreased protein expression of SP-A. Furthermore, exogenous SP administration to LA-4 cells inhibited the TGF-β1-induced upregulation of fibrotic markers.
Overall, these findings suggest a novel antifibrotic mechanism of SP-A in the development of lung
fibrosis, which indicates the therapeutic potential of the lung SP-A in preventing the development
of IPF.
Keywords: surfactant protein A; pulmonary fibrosis; transforming growth factor-β1; CRISPR/Cas9