Functional analysis of human fibrocytes derived from monocytes reveals their profibrotic phenotype through paracrine effects

Abe, Shuichi; Sato, Seidai; Aono, Yoshinori; Azuma, Momoyo; Kishi, Masami; Koyama, Kazuya; Takahashi, Naoki; Kagawa, Kozo; Kawano, Hiroshi; Nishioka, Yasuhiko

doi:10.2152/jmi.67.102

Cited by 10 publications

(15 citation statements)

References 35 publications

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“…Although the ability of fibrocytes to produce and secret type VII collagen remains unclear, they could represent a population of type VII collagen-expressing cells in PBMCs based on their morphology, protein expression profile, and responsiveness to TGF-β, as mentioned above. However, fibrocytes display a unique cell surface phenotype of collagen I + /CD11b + /CD13 + /CD34 + /CD45RO + /MHC class II + /CD86 + [23], whereas IF and RT-PCR evaluations in the present study demonstrated that cultured cells obtained from PBMCs expressing type VII collagen do not express CD45 and CD34. Therefore, fibrocytes would not be the main population of PBMCs expressing type VII collagen.…”

Section: Discussioncontrasting

confidence: 69%

Availability of mRNA Obtained from Peripheral Blood Mononuclear Cells for Testing Mutation Consequences in Dystrophic Epidermolysis Bullosa

Akasaka

Nakano

Sawamura

2021

IJMS

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Dystrophic epidermolysis bullosa (DEB) is an inheritable blistering disease caused by mutations in COL7A1, which encodes type VII collagen. To address the issue of genotype-phenotype correlations in DEB, analyzing the consequences of COL7A1 mutations using mRNA is indispensable. Herein we established a novel method for testing the effect of mutations in DEB using COL7A1 mRNA extracted from peripheral blood mononuclear cells (PBMCs). We investigated the consequences of four COL7A1 mutations (c.6573 + 1G > C, c.6216 + 5G > T, c.7270C > T and c.2527C > T) in three Japanese individuals with recessive DEB. The novel method detected the consequences of two recurrent COL7A1 mutations (c.6573 + 1G > C, c.6216 + 5G > T) and a novel COL7A1 mutation (c.7270C > T) accurately. In addition, it detected aberrant splicing resulting from a COL7A1 mutation (c.2527C > T) which was previously reported as a nonsense mutation. Furthermore, we revealed that type VII collagen-expressing cells in PBMCs have similar cell surface markers as mesenchymal stem cells; they were CD105+, CD29+, CD45−, and CD34−, suggesting that a small number of mesenchymal stem cells or mesenchymal stromal cells are circulating in the peripheral blood, which enables us to detect COL7A1 mRNA in PBMCs. Taken together, our novel method for analyzing mutation consequences using mRNA obtained from PBMCs in DEB will significantly contribute to genetic diagnoses and novel therapies for DEB.

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Section: Discussioncontrasting

confidence: 69%

Availability of mRNA Obtained from Peripheral Blood Mononuclear Cells for Testing Mutation Consequences in Dystrophic Epidermolysis Bullosa

Akasaka

Nakano

Sawamura

2021

IJMS

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“…Since mesenchymal cells participate to the development of pulmonary fibrosis [ 29 , 30 , 31 ], we assessed the effects of spiperone on these cell populations. Spiperone significantly reduced the population of MSCs in the lungs of mice in group 5 compared with group 2 on the 21st day of the experiment ( Figure 9 ).…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, a decrease in the activity of MSC differentiation into adipocytes, osteoblasts, chondrocytes, and fibrocytes was observed. Notably, cells such as fibrocytes produce collagen [ 31 ]. Another important aspect of the action of spiperone is associated with a decrease in the clonal activity of fibroblast progenitor cells in the following chronological order: in the bone marrow, blood, lungs ( Figure 10 and Figure S1 ).…”

Section: Discussionmentioning

confidence: 99%

Micellar Hyaluronidase and Spiperone as a Potential Treatment for Pulmonary Fibrosis

Скурихин

Мадонов²,

Першина

et al. 2021

IJMS

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Concentration of hyaluronic acid (HA) in the lungs increases in idiopathic pulmonary fibrosis (IPF). HA is involved in the organization of fibrin, fibronectin, and collagen. HA has been proposed to be a biomarker of fibrosis and a potential target for antifibrotic therapy. Hyaluronidase (HD) breaks down HA into fragments, but is a subject of rapid hydrolysis. A conjugate of poloxamer hyaluronidase (pHD) was prepared using protein immobilization with ionizing radiation. In a model of bleomycin-induced pulmonary fibrosis, pHD decreased the level of tissue IL-1β and TGF-β, prevented the infiltration of the lung parenchyma by CD16+ cells, and reduced perivascular and peribronchial inflammation. Simultaneously, a decrease in the concentrations of HA, hydroxyproline, collagen 1, total soluble collagen, and the area of connective tissue in the lungs was observed. The effects of pHD were significantly stronger compared to native HD which can be attributed to the higher stability of pHD. Additional spiperone administration increased the anti-inflammatory and antifibrotic effects of pHD and accelerated the regeneration of the damaged lung. The potentiating effects of spiperone can be explained by the disruption of the dopamine-induced mobilization and migration of fibroblast progenitor cells into the lungs and differentiation of lung mesenchymal stem cells (MSC) into cells of stromal lines. Thus, a combination of pHD and spiperone may represent a promising approach for the treatment of IPF and lung regeneration.

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“…The growing evidences highlights the role of eosinophils granules and fibroblast cells which are derived from immune cells [22,23]. In a mice model of asthma, it was shown that allergic protein of soybean enhances the eosinophilic inflammation and exacerbation of asthmatic pathophysiology [24].…”

Section: Introductionmentioning

confidence: 99%

“…Eosinophil peroxidase helps in protein nitration during allergic airway inflammation in a murine model [27]. It is now being accepted that, lots of stem cells or immune cells comes to the lungs during any injury or allergen challenge and there differentiate into FSP-1 positive fibroblasts cells [22,28]. How these fibroblast cells come to the lungs and affects tissue remodelling and fibrosis is still a big question and need extensive investigation.…”

Section: Introductionmentioning

confidence: 99%

Eosinophils Restrict Diesel Exhaust Particles-induced Cell Proliferation of Lung Epithelial A549 Cells via Interleukin-13 Mediated Mechanisms: Implications for Tissue Remodeling and Fibrosis

Niranjan

Muthukumaravel

Devaraju

et al. 2022

CCHTS

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Background: Diesel exhaust particulates (DEPs) affect lung physiology and cause serious damage to the lungs. A number of studies demonstrated that, eosinophils play a very important role in the development of tissue remodelling and fibrosis of lungs. However, the exact mechanism of pathogenesis of tissue remodelling and fibrosis is not known. Methods: Both in vitro and in vivo models were used in the study. HL-60 and A549 cells were used in the study. Balb/C mice of 8 to 12 weeks old were used for in vivo study. Cell viability by MTT assay, RNA isolation by tri reagent was accomplished. mRNA expression of inflammatory genes were accomplished by real time PCR or qPCR. Immunohistochemistry was done to asses the localization and expressions of proteins. One way ANOVA followed by post hoc test were done for the statistical analysis. Graph-Pad Prism software was used for statistical analysis. Results: We for the first time demonstrate that, Interleukin-13 plays a very important role in the development of tissue remodelling and fibrosis. We report that, diesel exhaust particles significantly induce eosinophils cell proliferation and interleukin-13 release in in vitro culture conditions. Supernatant collected from DEP-induced eosinophils cells significantly restrict cell proliferation of epithelial cells in response to exposure of diesel exhast particles. Furthermore, purified interleukin-13 decreases the proliferation of A549 cells, highliting the involvement of IL-13 in tissue remodeling. Notably, Etoricoxib (selective COX-2 inhibitor) did not inhibit DEP-triggered release of interleukin-13, suggesting another cell signalling pathway. The in vivo exposer of DEP to the lungs of mice, resulted in high level of eosinophils degranulation as depicted by the EPX-1 immunostaining and altered level of mRNA expressions of inflammatory genes. We also found that, a-SMA, fibroblast specific protein (FSP-1) has been changed in response to DEP in the mice lungs along with the mediators of inflammation. Conclusion: Altogether, we elucidated, the mechanistic role of eosinophils and IL-13 in the DEP-triggered proliferation of lungs cells thus providing an inside in the pathophysiology of tissue remodelling and fibrosis of lungs.

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Functional analysis of human fibrocytes derived from monocytes reveals their profibrotic phenotype through paracrine effects

Cited by 10 publications

References 35 publications

Availability of mRNA Obtained from Peripheral Blood Mononuclear Cells for Testing Mutation Consequences in Dystrophic Epidermolysis Bullosa

Availability of mRNA Obtained from Peripheral Blood Mononuclear Cells for Testing Mutation Consequences in Dystrophic Epidermolysis Bullosa

Micellar Hyaluronidase and Spiperone as a Potential Treatment for Pulmonary Fibrosis

Eosinophils Restrict Diesel Exhaust Particles-induced Cell Proliferation of Lung Epithelial A549 Cells via Interleukin-13 Mediated Mechanisms: Implications for Tissue Remodeling and Fibrosis

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