PDGFR? and ?SMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis.

ABSTRACT: Pulmonary fibrosis is characterized by pronounced collagen deposition and myofibroblast expansion, whose origin and plasticity remain elusive. We utilized a fate-mapping approach to investigate ?-smooth muscle actin (?SMA)+ and platelet-derived growth factor receptor ? (PDGFR?)+ cells in two lung fibrosis models, complemented by cell type-specific next-generation sequencing and investigations on human lungs. Our data revealed that ?SMA+ and PDGFR?+ cells mark two distinct mesenchymal lineages with minimal transdifferentiation potential during lung fibrotic remodeling. Parenchymal and perivascular fibrotic regions were populated predominantly with PDGFR?+ cells expressing collagen, while ?SMA+ cells in the parenchyma and vessel wall showed variable expression of collagen and the contractile protein desmin. The distinct gene expression profile found in normal conditions was retained during pathologic remodeling. Cumulatively, our findings identify ?SMA+ and PDGFR?+ cells as two separate lineages with distinct gene expression profiles in adult lungs. This cellular heterogeneity suggests that anti-fibrotic therapy should target diverse cell populations.

SUBMITTER: Biasin V 

PROVIDER: S-EPMC7189793 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature