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 β (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)-β signaling or to pericyte-like cells in the absence of TGF-β 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.

特发性肺纤维化（IPF）是一种慢性进行性间质性肺疾病，包括成纤维细胞灶（FF）。越来越多地认识到，FF中的胶原过度生成细胞（例如病理性成纤维细胞）的起源是周细胞。但是，肺的周细胞和IPF肺中的FF都尚未完全鉴定。在这项研究中检查的人肺周细胞（HuL-P）表达了两个代表性的周细胞标记；血小板衍生的生长因子受体β（PDGFRB）和硫酸软骨素蛋白聚糖4（CSPG4），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，在存在转化生长因子（TGF）-β信号传导的情况下，HuL-P细胞转变为肌成纤维细胞样细胞，而在没有TGF-β信号传导的情况下，HuL-P细胞转变为周细胞样细胞（周细胞-成纤维细胞转变）。另一方面，在这项研究中检测到的FF始终位于周围肺上皮和毛细血管内皮之间，它们的基膜在生理上是融合的。该定位是高度特异性的，因为存在于间隙之间的唯一细胞是周细胞。如所预期的，FF对于PDGFRB和CSPG4是免疫组织化学阳性的，这表明周细胞被激活以形成FF。我们还发现，通过双重沉默Bcl-xL加MCL1难以根除HuL-P细胞。