Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.
Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.
Lab Invest. 2021 May;101(5):625-635. doi: 10.1038/s41374-020-00524-y. Epub 2021 Jan 14.
Pericytes apposed to the capillary endothelium are known to stabilize and promote endothelial integrity. Recent studies indicate that lung pericytes play a prominent role in lung physiology, and they are involved in the development of various lung diseases including lung injury in sepsis, pulmonary fibrosis, asthma, and pulmonary hypertension. Accordingly, human lung pericyte studies are important for understanding the mechanistic basis of lung physiology and pathophysiology; however, human lung pericytes can only be cultured for a few passages and no immortalized human lung pericyte cell line has been established so far. Thus, our study aims to establish an immortalized human lung pericyte cell line. Developed using SV40 large T antigen lentivirus, immortalized pericytes exhibit stable SV40T expression, sustained proliferation, and have significantly higher telomerase activity compared to normal human lung pericytes. In addition, these cells retained pericyte characteristics, marked by similar morphology, and expression of pericyte cell surface markers such as PDGFRβ, NG2, CD44, CD146, CD90, and CD73. Furthermore, similar to that of primary pericytes, immortalized pericytes promoted endothelial cell tube formation and responded to different stimuli. Our previous data showed that friend leukemia virus integration 1 (Fli-1), a member of the ETS transcription factor family, is a key regulator that modulates inflammatory responses in mouse lung pericytes. We further demonstrated that Fli-1 regulates inflammatory responses in immortalized human lung pericytes. To summarize, we successfully established an immortalized human lung pericyte cell line, which serves as a promising tool for in vitro pericyte studies to understand human lung pericyte physiology and pathophysiology.
已知贴附于毛细血管内皮的周细胞能够稳定并促进内皮完整性。最近的研究表明,肺周细胞在肺生理学中发挥着重要作用,它们参与了多种肺部疾病的发展,包括脓毒症中的肺损伤、肺纤维化、哮喘和肺动脉高压。因此,人类肺周细胞的研究对于理解肺生理学和病理生理学的机制基础非常重要;然而,人类肺周细胞只能培养少数代,并且到目前为止还没有建立永生化的人类肺周细胞系。因此,我们的研究旨在建立永生化的人类肺周细胞系。使用 SV40 大 T 抗原慢病毒建立的永生化周细胞稳定表达 SV40T,持续增殖,端粒酶活性明显高于正常人类肺周细胞。此外,这些细胞保留了周细胞的特征,形态相似,并表达周细胞表面标志物,如 PDGFRβ、NG2、CD44、CD146、CD90 和 CD73。此外,与原代周细胞类似,永生化周细胞促进内皮细胞管形成,并对不同刺激做出反应。我们之前的数据表明,Friend 白血病病毒整合 1(Fli-1),ETS 转录因子家族的一员,是调节小鼠肺周细胞炎症反应的关键调节因子。我们进一步证明,Fli-1 调节永生化人肺周细胞的炎症反应。总之,我们成功建立了永生化的人类肺周细胞系,这为体外周细胞研究提供了一种有前途的工具,以了解人类肺周细胞的生理学和病理生理学。