Fibrocytes are involved in the pathogenesis of human chronic kidney disease

Sakai, Norihiko; Furuichi, Kengo; Shinozaki, Yukiko; Yokota, Hiroyuki; Toyama, Tadashi; Kitajima, Shinji; Okumura, Tomoko; Kokubo, Satoshi; Kobayashi, Motoo; Takasawa, Kazuya; Takeda, Shin‐ichi; Yoshimura, Mitsuhiro; Kaneko, Shuichi; Wada, Takashi

doi:10.1016/j.humpath.2009.10.008

Cited by 39 publications

(28 citation statements)

References 36 publications

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“…Fibrocytes are also found in the scar tissue-like lesions associated with fibrotic diseases such as pulmonary fibrosis, congestive heart failure, cirrhosis of the liver, and nephrogenic systemic fibrosis (3,(7)(8)(9)(10)(11). Fibrocytes express markers of both hematopoietic cells (CD34, CD45, FcγR, LSP-1, MHC class II) and stromal cells (collagens, fibronectin, and matrix metalloproteases) (2,3,(12)(13)(14).…”

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confidence: 99%

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

Pilling

Vakil

Cox

et al. 2015

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

109

103

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In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived fibroblast-like cells called fibrocytes help to form scar tissue. Although fibrocytes promote collagen production by fibroblasts, little is known about signaling from fibroblasts to fibrocytes. In this report, we show that fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that lumican, but not the related proteoglycan decorin, promotes human fibrocyte differentiation. Lumican competes with the serum fibrocyte differentiation inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors that affect fibrocyte differentiation, lumican has no detectable effect on macrophage differentiation or polarization. α2β1, αMβ2, and αXβ2 integrins are needed for lumican-induced fibrocyte differentiation. In lung tissue from pulmonary fibrosis patients with relatively normal lung function, lumican is present at low levels throughout the tissue, whereas patients with advanced disease have pronounced lumican expression in the fibrotic lesions. These data may explain why fibrocytes are increased in fibrotic tissues, suggest that the levels of lumican in tissues may have a significant effect on the decision of monocytes to differentiate into fibrocytes, and indicate that modulating lumican signaling may be useful as a therapeutic for fibrosis.

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mentioning

confidence: 99%

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

Pilling

Vakil

Cox

et al. 2015

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

109

103

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“…Cultured monocytes can differentiate into fibrocytes, but it is still unclear if maturation of fibrocytes occurs in the bone marrow, the circulation, or after migration to the tissues. Fibrocytes contribute to the innate response to injury and tissue remodeling, and these cells also mediate fibrogenesis in a number of systemic and organ-specific fibrosing disorders, such as renal fibrosis, 10 ischemic cardiomyopathy, 11,12 pulmonary fibrosis, 13,14 asthma, [15][16][17][18] and keloid scarring. 19 Recently, Abu El-Asrar et al 20,21 demonstrated that circulating fibrocytes contributed to the population of myofibroblasts in the epiretinal membranes of patients with PDR and iovs.arvojournals.org j ISSN: 1552-5783 proliferative vitreoretinopathy.…”

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confidence: 99%

Fibrocytes and Fibrovascular Membrane Formation in Proliferative Diabetic Retinopathy

Tamaki

Usui‐Ouchi

Murakami

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to investigate whether fibrocytes participate in formation of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR).METHODS. Vitreous fluid and FVM samples were obtained during vitrectomy in patients with PDR. Samples from patients with macular hole or epiretinal membrane were used as controls. Vitreous fluid and FVM samples were subjected to immunohistochemical analysis. In addition, cells isolated from the vitreous fluid of PDR and control patients were cultured in serum-free medium. Fibrocytes were identified among these cells by morphological and immunohistochemical analyses. We examined the number of fibrocytes in PDR patients and control patients. Also, the concentrations of monocyte chemoattractant protein-1 (MCP-1), pentraxin3, and serum amyloid P (SAP) in vitreous fluid samples from PDR patients and control patients were determined by enzyme-linked immunosorbent assay.RESULTS. Fibrocytes were observed in the vitreous and FVM samples from PDR patients. Cells cultured from the vitreous samples of PDR patients were spindle shaped and expressed fibrocyte markers. TGF-b1 induced differentiation of these cells into myofibroblasts. The number of fibrocytes was higher in samples from PDR patients than in samples from control patient. The vitreous fluid concentration of MCP-1 was significantly higher in PDR patients than in controls and showed a significant positive correlation with the number of fibrocytes from the vitreous fluid. Vitreous fluid concentrations of pentraxin3 and SAP were also higher in PDR patients than in control patients.CONCLUSIONS. These findings indicate that fibrocytes may be involved in development of the FVM in PDR.

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“…Fibrocytes are also found in lesions associated with fibrotic diseases such as pulmonary fibrosis, congestive heart failure, cirrhosis of the liver, and nephrogenic systemic fibrosis (3,(5)(6)(7)(8)(9). Fibrocytes express markers of both hematopoietic cells (CD34, CD45, FcγR, LSP-1, and MHC class II) and stromal cells (collagens, fibronectin, and matrix metalloproteases) (2,3,(10)(11)(12).…”

mentioning

confidence: 99%

Fibroblasts secrete Slit2 to inhibit fibrocyte differentiation and fibrosis

Pilling

Zheng

Vakil

et al. 2014

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

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Significance A key question in fibrosing diseases is why monocytes do not become fibrocytes in healthy tissues but can become fibrocytes in fibrotic lesions. We show that fibroblasts secrete a signal that inhibits the differentiation of monocytes into fibrocytes. We identify the signal as Slit2 and show that Slit2 levels are low in fibrotic lesions. We also show that injection of Slit2 prevents fibrosis in a mouse model of lung fibrosis. The identification of Slit2 as a key signal in normal tissues that prevents entering monocytes from becoming fibrocytes represents a major advance in our understanding of the regulation of the innate immune system and how fibrosis propagates, as well as a potential novel therapeutic for fibrosis.

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Fibrocytes are involved in the pathogenesis of human chronic kidney disease

Cited by 39 publications

References 36 publications

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

Fibrocytes and Fibrovascular Membrane Formation in Proliferative Diabetic Retinopathy

Fibroblasts secrete Slit2 to inhibit fibrocyte differentiation and fibrosis

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