Circulating Fibrocytes—Biology and Mechanisms in Wound Healing and Scar Formation

Grieb, Gerrit; Steffens, Gerd; Pallua, Norbert; Bernhagen, Jürgen; Bucala, Richard

doi:10.1016/b978-0-12-386035-4.00001-x

Cited by 96 publications

(76 citation statements)

References 80 publications

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“…The term "fibrocyte" was originally used by Kaye et al (45) to describe the fibroblast-like cells they saw at the top of the crypt, which they described as "differentiated and functioning fibroblasts" that could not divide and produce collagen at the same time. More recently, the term has been used for a quite different type of cell that combines fibroblast or MF-like characteristics with hematopoietic properties, including the expression of CD45 (46). These cells may play an important role in immune responses in the tumor microenvironment (47).…”

Section: Discussionmentioning

confidence: 99%

Myofibroblasts are distinguished from activated skin fibroblasts by the expression of AOC3 and other associated markers

Hsia

Ashley

Ouaret

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumor progression. Myofibroblasts previously have been distinguished from normal fibroblasts mostly by the expression of α smooth muscle actin (αSMA). We now have identified AOC3 (amine oxidase, copper containing 3), a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast-reacting mAb PR2D3. The normal and tumor tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used for FACS sorting of myofibroblasts obtained by nonenzymatic procedures. Whole-genome microarray mRNA-expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly differentially expressed in these two cell types: NKX2-3 and LRRC17 in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts. TGFβ substantially down-regulated AOC3 expression in myofibroblasts but in skin fibroblasts it dramatically increased the expression of αSMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of myofibroblast-related gene expression and increased expression of the fibroblast-associated gene SHOX2, suggesting that NKX2-3 is a key mediator for maintaining myofibroblast characteristics. Our results show that colorectal myofibroblasts, as defined by the expression of AOC3, NKX2-3, and other markers, are a distinctly different cell type from TGFβ-activated fibroblasts.myofibroblasts | α smooth muscle actin | tumor microenvironment | AOC3 | NKX2-3

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Section: Discussionmentioning

confidence: 99%

Myofibroblasts are distinguished from activated skin fibroblasts by the expression of AOC3 and other associated markers

Hsia

Ashley

Ouaret

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Derived from bone marrow, circulating fibrocytes exist in the peripheral circulation and migrate with the peripheral blood to wound chambers in response to chemokines [12]. Activated circulating fibrocytes not only secrete ECM, which is essential for the process of fibrosis, but also lead to pathological fibrosis by differentiating to (myo) fibroblasts [13]. This prompted us to investigate whether targeting circulating fibrocytes could open up a new avenue for resolving fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Treatment Suppresses CCR7 Expression and the Differentiation and Migration of Human Circulating Fibrocytes

Fu¹,

Zhang²,

Li³

et al. 2015

Cell Physiol Biochem

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Background/Aim: Recent studies have demonstrated that circulating fibrocytes contribute to the formation and development of fibrosis. Curcumin, a polyphenolic compound isolated from turmeric, has been shown to have anti-fibrotic effects in various organs. We and others have demonstrated that curcumin beneficially affects the development of fibrosis. However the effect of curcumin on circulating fibrocytes has not been reported. Methods: Human circulating fibrocytes were isolated from leukocyte concentrates of healthy human donors and identified based on the expression of CD34, CD45, collagen I (COLI), and chemokine receptor CCR7 (CCR7) via flow cytometry. Cell Counting Kit-8 was used to evaluate cell viability. The effect of curcumin on the differentiation and migration of human circulating fibrocytes was evaluated by immunofluorescence staining, flow cytometry and a transwell migration assay. Transforming growth factor (TGF)-β1 secretion was examined by ELISA. Results: Curcumin treatment (72 h; 20 μM) significantly decreased the expression of COL I, α-SMA and CCR7, as well as TGF-βl secretion, in human circulating fibrocytes. The inhibitory effect of curcumin on the differentiation and migration of human circulating fibrocytes is likely via regulating the CCR7/CCL21 signaling pathway, in particular by reducing CCR7 expression. These observed effects may be beneficial in resolving fibrosis by suppressing TGF-β1 secretion. Conclusion: Our results suggest that curcumin has the potential to suppress the differentiation and migration of circulating fibrocytes, which would provide new explanation for curcumin's application in the development of fibrosis in various organs.

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“…In addition, IFN-a 2b has also been shown to inhibit TGF-b-induced alpha smooth muscle actin expression in a unique subpopulation of leukocytes known as fibrocytes, 124 which are circulating bone marrow derived cells that can leave the blood, enter tissues, and differentiate into myofibroblasts in response to TGF-b. 125 Interestingly, dermal fibroblasts treated with conditioned medium (CM) from burn patient fibrocytes (but not by CM from normal fibrocytes) showed an increase in proliferation, migration, and contractility, which was abrogated by application of a TGF-b1 neutralizing antibody. 126 These findings suggest that fibrocytes in burn patients may act as a source of systemic TGF-b1 as well as a target for TGF-b1-induced myofibroblast differentiation action in tissues, thereby creating a vicious cycle of TGF-b1 production and action in pathogenesis of HTS.…”

mentioning

confidence: 99%

Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

Finnson

McLean

Guglielmo

et al. 2013

Advances in Wound Care

247

222

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Circulating Fibrocytes—Biology and Mechanisms in Wound Healing and Scar Formation

Cited by 96 publications

References 80 publications

Myofibroblasts are distinguished from activated skin fibroblasts by the expression of AOC3 and other associated markers

Myofibroblasts are distinguished from activated skin fibroblasts by the expression of AOC3 and other associated markers

Curcumin Treatment Suppresses CCR7 Expression and the Differentiation and Migration of Human Circulating Fibrocytes

Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

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