载脂蛋白E
博莱霉素
LRP1型
巨噬细胞
肺纤维化
肺
单核细胞
纤维化
肌成纤维细胞
特发性肺纤维化
医学
发病机制
免疫学
病理
化学
脂蛋白
内科学
低密度脂蛋白受体
体外
胆固醇
生物化学
化疗
疾病
作者
Huachun Cui,Dechun Jiang,Sami Banerjee,Na Xie,Tejaswini Kulkarni,Rui-Ming Liu,Steven R. Duncan,Gang Liu
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2020-03-12
卷期号:5 (5)
被引量:41
标识
DOI:10.1172/jci.insight.134539
摘要
Recent studies have presented compelling evidence that it is not tissue-resident, but rather monocyte-derived alveolar macrophages (TR-AMs and Mo-AMs, respectively) that are essential to development of experimental lung fibrosis. However, whether apolipoprotein E (ApoE), which is produced abundantly by Mo-AMs in the lung, plays a role in the pathogenesis is unclear. In this study, we found that pulmonary ApoE was almost exclusively produced by Mo-AMs in mice with bleomycin-induced lung fibrosis. We showed that, although ApoE was not necessary for developing maximal fibrosis in bleomycin-injured lung, it was required for the resolution of this pathology. We found that ApoE directly bound to Collagen I and mediated Collagen I phagocytosis in vitro and in vivo, and this process was dependent on low-density lipoprotein receptor–related protein 1 (LPR1). Furthermore, interference of ApoE/LRP1 interaction impaired the resolution of lung fibrosis in bleomycin-treated WT mice. In contrast, supplementation of ApoE promoted this process in ApoE–/– animals. In conclusion, Mo-AM–derived ApoE is beneficial to the resolution of lung fibrosis, supporting the notion that Mo-AMs may have distinct functions in different phases of lung fibrogenesis. The findings also suggest a potentially novel therapeutic target for treating lung fibrosis, to which effective remedies remain scarce.
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