Pericyte-myofibroblast transition in the human lung

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. • Human lung pericytes (HuL-P) express PDGFRB and CSPG4, markers for pericytes. • HuL-P cells stimulated by TGF-β signaling transition to myofibroblast-like cells. • PDGFRB and CSPG4 are expressed in fibroblastic foci (FF) in lungs with fibrosis. • Pericytes activated by TGF-β signaling would transition to myofibroblasts in FF. • Suppression of pericyte-myofibroblast transition could mitigate pulmonary fibrosis.