FGF2, an Immunomodulatory Factor in Asthma and Chronic Obstructive Pulmonary Disease (COPD)

Tan, Yuan-Yang; Qiao, Yong‐Kang; Chen, Zhuang‐Gui; Liu, Jing; Guo, Yanrong; Tran, Thai; Tan, Kai Sen; Wang, Deyun; Yan, Yan

doi:10.3389/fcell.2020.00223

Cited by 34 publications

(26 citation statements)

References 127 publications

(166 reference statements)

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“…Although all molecular locations have distinct and important functions in cellular processes, we can see that extracellular molecules act more negatively in skin wound healing when silenced ( Figure 6 ), probably because they act as signals for several important metabolic pathways. In addition, some molecules that have different locations may do different functions depending on their location and not participate in repair-related metabolic pathways, for example, bFGF in the extracellular space acts on metabolic pathways that result in cell proliferation, migration, differentiation, and apoptosis, while in the intracellular environment, this molecule acts on antiviral immunity [ 104 ].…”

Section: Discussionmentioning

confidence: 99%

What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence

Nogueira

Campos

Alves

et al. 2020

Oxidative Medicine and Cellular Longevity

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Cytokines and growth factors are known to play an important role in the skin wound closure process; however, in knockout organisms, the levels of these molecules can undergo changes that result in the delay or acceleration of this process. Therefore, we systematically reviewed evidence from preclinical studies about the main immunoregulatory molecules involved in skin repair through the analysis of the main mechanisms involved in the depletion of immunoregulatory genes, and we carried out a critical analysis of the methodological quality of these studies. We searched biomedical databases, and only original studies were analyzed according to the PRISMA guidelines. The included studies were limited to those which used knockout animals and excision or incision wound models without intervention. A total of 27 studies were selected; data for animal models, gene depletion, wound characteristics, and immunoregulatory molecules were evaluated and compared whenever possible. Methodological quality assessments were examined using the ARRIVE and SYRCLE’s bias of risk tool. In our review, the extracellular molecules act more negatively in the wound healing process when silenced and the metabolic pathway most affected involved in these processes was TGF-β/Smad, and emphasis was given to the importance of the participation of macrophages in TGF-β signaling. Besides that, proinflammatory molecules were more evaluated than anti-inflammatory ones, and the main molecules evaluated were, respectively, TGF-β1, followed by VEGF, IL-6, TNF-α, and IL-1β. Overall, most gene depletions delayed wound healing, negatively influenced the concentrations of proinflammatory cytokines, and consequently promoted a decrease of inflammatory cell infiltration, angiogenesis, and collagen deposition, compromising the formation of granulation tissue. The studies presented heterogeneous data and exhibited methodological limitations; therefore, mechanistic and highly controlled studies are required to improve the quality of the evidence.

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Section: Discussionmentioning

confidence: 99%

What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence

Nogueira

Campos

Alves

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Fgf2 expression was detected in macrophages and T-cells, both players in acute and chronic inflammation (Song et al, 2015;Shao et al, 2017). Several human studies revealed that FGF2 blood level is increased in Crohn's disease and ulcerative colitis patients (Kanazawa et al, 2001) and that FGF2 could induce the expression of several proinflammatory genes in asthma (Tan et al, 2020). In inflammatory bowel disease (IBD) pathogenesis, the role of the inflammatory cytokines and the cells that produce them, T-helper1 and regulatory T-cells (specifically γδ T-cells), are well recognized.…”

Section: Fgf2 and Inflammationmentioning

confidence: 99%

“…Other studies dealing with lung diseases suggest that FGF2 may be associated with airway inflammation, bringing up the possibility of FGF2-targeted therapy. A recent review summarized the role of FGF2 as an immunomodulatory factor in COPD and severe asthma (Tan et al, 2020). In lung diseases, the inflammatory component is often responsible for the exacerbation of the pathology.…”

Section: Fgf2 and Inflammationmentioning

confidence: 99%

Cross-Talk Between Inflammation and Fibroblast Growth Factor 10 During Organogenesis and Pathogenesis: Lessons Learnt From the Lung and Other Organs

Marega

Chen

Bellusci

2021

Front. Cell Dev. Biol.

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The adult human lung is constantly exposed to irritants like particulate matter, toxic chemical compounds, and biological agents (bacteria and viruses) present in the external environment. During breathing, these irritants travel through the bronchi and bronchioles to reach the deeper lung containing the alveoli, which constitute the minimal functional respiratory units. The local biological responses in the alveoli that follow introduction of irritants need to be tightly controlled in order to prevent a massive inflammatory response leading to loss of respiratory function. Cells, cytokines, chemokines and growth factors intervene collectively to re-establish tissue homeostasis, fight the aggression and replace the apoptotic/necrotic cells with healthy cells through proliferation and/or differentiation. Among the important growth factors at play during inflammation, members of the fibroblast growth factor (Fgf) family regulate the repair process. Fgf10 is known to be a key factor for organ morphogenesis and disease. Inflammation is influenced by Fgf10 but can also impact Fgf10 expression per se. Unfortunately, the connection between Fgf10 and inflammation in organogenesis and disease remains unclear. The aim of this review is to highlight the reported players between Fgf10 and inflammation with a focus on the lung and to propose new avenues of research.

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“…Another example of ECM bound factor is fibroblast growth factor (FGF)-2, which binds on a nanomolar level to HS ( Ibrahimi et al, 2004 ). This GAG-growth factor complex increases the binding to the FGF receptor 1 and is crucial for adequate cell signaling ( Yayon et al, 1991 ) and may be immunomodulatory factor in COPD ( Tan et al, 2020 ). Therefore, the ECM and growth factor complexes works to fine-tune cell responses and control timing, making it an important target in the development of therapies in chronic lung diseases.…”

Section: The Intrinsic Properties Of the Lung-ecmmentioning

confidence: 99%

Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

et al. 2021

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It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal stromal/stem cells (MSC) have been shown to have immunomodulatory properties and may be potent actors regulating tissue remodelling and regenerative cell responses upon lung injury. Using MSC in cell-based therapy holds promise for treatment of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, so far clinical trials with MSCs in COPD have not had a significant impact on disease amelioration nor on IPF, where low cell survival rate and pulmonary retention time are major hurdles to overcome. Research shows that the microenvironment has a profound impact on transplanted MSCs. In our studies on acellular lung tissue slices (lung scaffolds) from IPF patients versus healthy individuals, we see a profound effect on cellular activity, where healthy cells cultured in diseased lung scaffolds adapt and produce proteins further promoting a diseased environment, whereas cells on healthy scaffolds sustain a healthy proteomic profile. Therefore, modulating the environmental context for cell-based therapy may be a potent way to improve treatment using MSCs. In this review, we will describe the importance of the microenvironment for cell-based therapy in chronic lung diseases, how MSC-ECM interactions can affect therapeutic output and describe current progress in the field of cell-based therapy.

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FGF2, an Immunomodulatory Factor in Asthma and Chronic Obstructive Pulmonary Disease (COPD)

Cited by 34 publications

References 127 publications

What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence

What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence

Cross-Talk Between Inflammation and Fibroblast Growth Factor 10 During Organogenesis and Pathogenesis: Lessons Learnt From the Lung and Other Organs

Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

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