The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of pulmonary fibrosis - PubMed (original) (raw)

Review

The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of pulmonary fibrosis

Robert M Strieter et al. J Leukoc Biol. 2009 Nov.

Abstract

Pulmonary fibrosis is associated with a number of disorders that affect the lung. Although there are several cellular types that are involved in the pathogenesis pulmonary fibrosis, the resident lung fibroblast has been viewed traditionally as the primary cell involved in promoting the deposition of ECM that culminates in pulmonary fibrosis. However, recent findings demonstrate that a circulating cell (i.e., the fibrocyte) can contribute to the evolution of pulmonary fibrosis. Fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of cell-surface markers related to leukocytes, hematopoietic progenitor cells, and fibroblasts. Fibrocytes are unique in that they are capable of differentiating into fibroblasts and myofibroblasts, as well as adipocytes. In this review, we present data supporting the critical role these cells play in the pathogenesis of pulmonary fibrosis.

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Figures

Figure 1.

Figure 1.

Cartoon demonstrating the different signaling pathways that participate in fibrocyte differentiation into αSMA-expressing myofibroblasts or differentiation into aP2-expressing adipocytes. Signaling pathways activated by TGF-β1, including Smad2/3 and stress-activated protein kinases/JNK MAPK, collaborate to induce αSMA transcription, whereas Troglitazone (TGZ)-mediated PPARγ activation leads to induction of aP2 expression. The cross-talk and complex balance of TGF-β with PPARγ signaling, within the context of the local microenvironmental niche, drive the selection of defined differentiation pathways. TβRII/I, TGF-β type II/I receptor; DAXX, death-associated protein 6; TAK1, TGF-β-activated kinase 1; ATF2, activating transcription factor 2; SRE, Smad response element; PPRE, peroxisome proliferator response element; RXR, retinoid X receptor.

Figure 2.

Figure 2.

Cartoon demonstrating the signaling pathways for the up-regulation of CXCR4 expression on fibrocytes related to the role of hypoxia and activation of the PI3K/AKT/mTOR pathway that culminates in promoting trafficking of CXCR4+ fibrocytes to the lung in response to CXCL12. VHL, Von Hippel-Lindau; GF, growth factor.

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