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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / adverse effects*
  • Forkhead Transcription Factors / drug effects*
  • Lung Injury / chemically induced*
  • Lung Injury / pathology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Myofibroblasts / drug effects
  • Pericytes / drug effects
  • Pericytes / pathology*
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / pathology*


  • Forkhead Transcription Factors
  • Foxd1 protein, mouse
  • Bleomycin