Pericyte-myofibroblast transition in the human lung
Pericyte-myofibroblast transition in the human lung
复制标题
DOI：
10.1016/j.bbrc.2020.05.091
复制
发表时间：
2020-07-23
影响因子：
3.1
通讯作者：
Sakuma, Yuji
中科院分区：
文献类型：
--
作者：
Yamaguchi, Miki;Hirai, Sachie;Sakuma, Yuji
特发性肺纤维化（IPF）是一种慢性、进行性间质性肺病，包括成纤维细胞病灶（FF）。越来越多的人认识到，FF中胶原过度产生细胞如病理性肌成纤维细胞的起源是周细胞。然而，来自肺的周细胞和IPF肺中的FF均未得到充分表征。在本研究中检查的人肺周细胞（HuL-P）表达两种代表性的周细胞标志物;血小板衍生生长因子受体β（PDGFRB）和硫酸软骨素蛋白聚糖4（CSPG 4），并且能够在3D条件下迁移并覆盖内皮管，表明它们保留了周细胞的特征。此外，HuL-P细胞在存在转化生长因子（TGF）-β信号传导的情况下转变为成肌纤维细胞样细胞，或在不存在TGF-β信号传导的情况下转变为周细胞样细胞（周细胞-成肌纤维细胞转变）。另一方面，在本研究中检测到的FF总是位于外周肺上皮细胞和毛细血管内皮细胞之间，其基底膜在生理上是融合的。定位是高度特异性的，因为存在于差距之间的唯一细胞是周细胞。正如预期的，FF对PDGFRB和CSPG 4呈免疫化学阳性，表明周细胞被激活以形成FF。我们还发现，HuL-P细胞难以通过Bcl-xL加MCL 1的双重沉默来根除。对于IPF的治疗，抑制周细胞-肌成纤维细胞转变比杀死活化的肌成纤维细胞更明智。(C)2020爱思唯尔公司All rights reserved.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease that includes fibroblastic foci (FF). It has been increasingly appreciated that the origin of collagen-overproducing cells such as pathological myofibroblasts in FF is pericytes. However, neither pericytes derived from the lung nor FF in the IPF lung have not been fully characterized. Human lung pericytes (HuL-P) examined in this study expressed two representative pericyte markers; platelet-derived growth factor receptor beta (PDGFRB) and chondroitin sulfate proteoglycan 4 (CSPG4), and were able to migrate and cover endothelial tubes in 3D conditions, indicating that they retain characteristics of pericytes. Moreover HuL-P cells transitioned to myofibroblast-like cells in the presence of transforming growth factor (TGF)-beta signaling or to pericyte-like cells in the absence of TGF-beta signaling (pericyte-myofibroblast transition). On the other hand, the FF detected in this study were invariably localized between peripheral lung epithelia and capillary endothelia, the basement membranes of which are physiologically fused. The localization is highly specific in that the only cells that exist between the gap are pericytes. As expected, FF were immunohistochemically positive for PDGFRB and CSPG4, suggesting that pericytes are activated to form FF. We also found that HuL-P cells were difficult to eradicate by dual silencing of Bcl-xL plus MCL1. It would be more sensible to suppress pericyte-myofibroblast transition than to kill activated myofibroblasts for the treatment of IPF. (C) 2020 Elsevier Inc. All rights reserved.