抽象的
Introduction:在肺动脉高压(PAH)中,目前的疗法不靶向肺血管重塑(PVR),这是该疾病的主要原因。I型细胞因子受体(TypeIR)已知在PAH肺动脉平滑肌细胞(PA-SMC)中过表达,并参与PVR。
Aims and Objectives:To assess whether the regulation of TypeIR intracellular trafficking is altered in PAH, leading to TypeIR overexpression and PVR.
方法:We studied TypeIR trafficking through the main regulatory proteins ubiquitin-specific protease 8 (USP8) and ring finger protein (RNF)41. In PAH patients and in controls, we performed in situ immunostaining in lung samples and western blotting in primary cultures of PA-SMCs isolated from human tissues. We transfected human PA-SMCs with siRNA against USP8 and RNF41 in vitro. In two experimental models, the monocrotaline- and chronic hypoxia-induced PAH, we performed hemodynamic measurements followed by in situ immunostaining and western blotting analysis in lung tissues.
Results:We showed an increased USP8 and decreased RNF41 expression in PAH lungs compared to controls, and a similar shift in USP8/RNF41 ratio at the protein level in PAH PA-SMCs compared to controls (n=10). We modulated USP8/RNF41 ratio with siRNAs and restored TypeIR expression and its signalling (n=5). Consistent with our human in situ and in vitro results, we confirmed the altered USP8/RNF41 ratio in the two in vivo models (n=8 and n=5).
结论:与对照组相比,PAH患者的细胞内运输调节发生了变化,这是由于USP8/RNF41比率的变化。恢复PA-SMC中的USP8/RNF41比率可能代表PAH的潜在目标。
脚注
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3557.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available atwww.ers-education.org(ERS member access only).
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