缺陷的 CSF2RA 导致 SMDP4
中文名称
通路描述
肺泡巨噬细胞对表面活性物质的分解在表面活性物质的回收和代谢中起着虽小但关键的作用。在配体结合后，粒细胞 - 巨噬细胞集落刺激因子受体 (GM-CSFR)，由α (CSF2RA) 和β (CSF2RB) 亚基组成的异二聚体，启动了一个信号传导过程，不仅诱导造血细胞的增殖、分化和功能激活，还可以决定表面活性物质被吸入肺泡巨噬细胞并通过氯仿包被小泡进行降解。人类 CSF2RA 缺陷可导致肺表面活性物质代谢功能障碍 4 (SMDP4; MIM:300770，即先天性肺泡蛋白沉积症 (PAP))，这是一种罕见的肺部疾病，由于表面活性物质稳态受损而致病，其特征是肺泡充满团状物质。对错误折叠的 pro-SFTPC 产物的细胞反应包括内质网应激、活性氧激活和自噬。肺泡内过量脂蛋白积累导致早产儿的一种呼吸窘迫综合征 (RDS; MIM:267450) (Whitsett et al. 2015)。
英文描述
Defective CSF2RA causes SMDP4 Surfactant catabolism by alveolar macrophages plays a small but critical part in surfactant recycling and metabolism. Upon ligand binding, granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), a heterodimer of alpha (CSF2RA) and beta (CSF2RB) subunits, initiates a signalling process that not only induces proliferation, differentiation and functional activation of hematopoietic cells but can also determine surfactant uptake into alveolar macrophages and its degradation via clathrin-coated vesicles. Defects in human CSF2RA can cause pulmonary surfactant metabolism dysfunction 4 (SMDP4; MIM:300770, aka congenital pulmonary alveolar proteinosis, (PAP)), a rare lung disorder due to impaired surfactant homeostasis characterised by alveoli filling with floccular material. Cellular responses to the misfolded pro-SFTPC products include ER stress, the activation of reactive oxygen species and autophagy. Excessive lipoprotein accumulation in the alveoli results in a form of respiratory distress syndrome in premature infants (RDS; MIM:267450) (Whitsett et al. 2015).
所含基因
7 个基因