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Am J Respir Crit Care Med. 2013 Oct 1;188(7):820-30. doi: 10.1164/rccm.201212-2297OC.

Role of lung pericytes and resident fibroblasts in the pathogenesis of pulmonary fibrosis.

Author information

1
1 Center for Lung Biology, Pulmonary and Critical Medicine.

Abstract

RATIONALE:

The origin of cells that make pathologic fibrillar collagen matrix in lung disease has been controversial. Recent studies suggest mesenchymal cells may contribute directly to fibrosis.

OBJECTIVES:

To characterize discrete populations of mesenchymal cells in the normal mouse lung and to map their fate after bleomycin-induced lung injury.

METHODS:

We mapped the fate of Foxd1-expressing embryonic progenitors and their progeny during lung development, adult homeostasis, and after fibrosing injury in Foxd1-Cre; Rs26-tdTomato-R mice. We studied collagen-I(α)1-producing cells in normal and diseased lungs using Coll-GFP(Tg) mice.

MEASUREMENTS AND MAIN RESULTS:

Foxd1-expressing embryonic progenitors enter lung buds before 13.5 days post-conception, expand, and form an extensive lineage of mesenchymal cells that have characteristics of pericytes. A collagen-I(α)1-expressing mesenchymal population of distinct lineage is also found in adult lung, with features of a resident fibroblast. In contrast to resident fibroblasts, Foxd1 progenitor-derived pericytes are enriched in transcripts for innate immunity, vascular development, WNT signaling pathway, and cell migration. Foxd1 progenitor-derived pericytes expand after bleomycin lung injury, and activate expression of collagen-I(α)1 and the myofibroblast marker αSMA in fibrotic foci. In addition, our studies suggest a distinct lineage of collagen-I(α)1-expressing resident fibroblasts that also expands after lung injury is a second major source of myofibroblasts.

CONCLUSIONS:

We conclude that the lung contains an extensive population of Foxd1 progenitor-derived pericytes that are an important lung myofibroblast precursor population.

PMID:
23924232
PMCID:
PMC3826269
DOI:
10.1164/rccm.201212-2297OC
[Indexed for MEDLINE]
Free PMC Article

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