期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 184, 期 5, 页码 1369-1383出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2014.01.012
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资金
- National Heart, Lung, and Blood Institute [R01 HL074882, P01 HL91775, R01 FIL089249]
- O'Brien family
- Swedish Research Council
- National Center for Advancing Translational Sciences of the National Institutes of Health [8UL1TR000114-02]
- Flow Cytometry Core Facility of the Masonic Cancer Center
- National Cancer Institute [P30 CA77598]
- University of Minnesota Imaging Center
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the middle aged and elderly with a prevalence of one million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli, creating a reticular network that Leads to death by asphyxiation. Lung fibroblasts from patients with IPF have phenotypic hallmarks, distinguishing them from their normal counterparts: pathologically activated Akt signaling axis, increased collagen and alpha-smooth muscle actin expression, distinct gene expression profile, and ability to form fibrotic lesions in model. organisms. Despite the centrality of these fibroblasts in disease pathogenesis, their origin remains uncertain. Here, we report the identification of cells in the lungs of patients with IPF with the properties of mesenchymal progenitors. In contrast to progenitors isolated from nonfibrotic Lungs, IPF mesenchymal progenitor cells produce daughter cells manifesting the full spectrum of IPF hallmarks, including the ability to form fibrotic Lesions in zebrafish embryos and mouse lungs, and a transcriptional profile reflecting these properties. Morphological analysis of IPF Lung tissue revealed that mesenchymal progenitor cells and cells with the characteristics of their progeny comprised the fibrotic reticulum. These data establish that the Lungs of patients with IPF contain pathological mesenchymal progenitor cells that are cells of origin for fibrosis-mediating fibroblasts. These fibrogenic mesenchymal progenitors and their progeny represent an unexplored target for novel therapies to interdict fibrosis.
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