GATA1-defective immune-megakaryocytes as possible drivers of idiopathic pulmonary fibrosis.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disorder with limited therapeutic options. Insufficient understanding of driver mutations and poor fidelity of currently available animal models has limited the development of effective therapies. Since GATA1 deficient megakaryocytes sustain myelofibrosis, we hypothesized that they may also induce fibrosis in lungs. We discovered that lungs from IPF patients and Gata1^low mice contain numerous GATA1negative immune-poised megakaryocytes that, in mice, have defective RNA-seq profiling and increased TGF-β1, CXCL1 and P-selectin content. With age, Gata1^low mice develop fibrosis in lungs. Development of lung fibrosis in this model is prevented by P-selectin deletion and res

SUBMITTER: Gobbo F 

PROVIDER: S-EPMC10327123 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature