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IL-33, a new member of the IL-1F, is widely expressed throughout the body and can be up-regulated by stimulation with proinflammatory factors. It has been identified as a functional ligand for the plasma membrane receptor complex ...
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IL-33, a new member of the IL-1F, is widely expressed throughout the body and can be up-regulated by stimulation with proinflammatory factors. It has been identified as a functional ligand for the plasma membrane receptor complex that is a heterodimer consisting of membrane-bound ST2L, which is a member of the IL-1R family, and IL-1RAcP. IL-33 is crucial for the induction of Th2 immune responses. Additionally, under other circumstances, it can also act as an endogenous danger signal. Recently, many studies have demonstrated that IL-33 may be related to the development and progression of fibrotic diseases. It has proinflammatory effects in some fibrotic diseases but has anti-inflammatory effects in others. In this review, the biologic characteristics of IL-33 and the role of the IL-33/ST2 signaling pathway in various fibrotic diseases will be discussed. We hope this overview will provide new insights for the treatment of these diseases.
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Apelin, an endogenous ligand of the G-protein-coupled receptor APJ, is expressed in a diverse number of organs. The apelin-APJ axis helps to control the processes of pathological and physiological fibrosis, including renal fibrosi...
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Apelin, an endogenous ligand of the G-protein-coupled receptor APJ, is expressed in a diverse number of organs. The apelin-APJ axis helps to control the processes of pathological and physiological fibrosis, including renal fibrosis, cardiac fibrosis, liver fibrosis and pulmonary fibrosis. However, the role of apelin-APJ in organ fibrosis remains controversial due to conflicting study results. The apelin-APJ axis is a detrimental mechanism which promotes liver fibrosis mainly via up-regulation the expression of collagen-II and platelet-derived growth factor receptor beta, (PDGFR beta). On the contrary, the apelin-APJ axis is beneficial for renal fibrosis, cardiac fibrosis and pulmonary fibrosis. The apelin-APJ axis alleviates renal fibrosis by restraining the expression of transforming growth factor-beta 1 (TGF-beta 1). In addition, the apelin-APJ axis attenuates cardiac fibrosis through multiple pathways. Furthermore, the apelin-APJ axis has beneficial effects on experimental bronchopulmonary dysplasia (BPD) and acute respiratory distress syndrome (ARDS) which suggest the apelin-APJ axis potentially alleviates pulmonary fibrosis. In this article, we review the controversies associated with apelin-APJ in organ fibrosis and introduce the drugs that target apelin-APJ. We conclude that future studies should place more emphasis on the relationship among apelin isoforms, APJ receptor subtypes and organ fibrosis. The apelin-APJ axis will be a potential therapeutic target and those drugs targeted for apelin-APJ may constitute a novel therapeutic strategy for renal fibrosis, cardiac fibrosis, liver fibrosis and pulmonary fibrosis. (C) 2016 Elsevier B.V. All rights reserved.
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High-mobility group box 1 (HMGB1) is originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can b...
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High-mobility group box 1 (HMGB1) is originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be passively released from necrotic cells or actively secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 is a multifunctional cytokine that contributes to the process of infection, injury, inflammation, apoptosis, and immune responses by binding to specific cell-surface receptors. Recently, emerging studies indicate that HMGB1 is closely involved in fibrotic disorders including cystic fibrosis, liver fibrosis and pulmonary fibrosis, while HMGB1 signal inhibitions protect against the experimental models of fibrotic diseases. From a clinical perspective, HMGB1 represents a current challenge that can be exploited orchestrate reparative responses. This review focuses on the crucial role of HMGB1 in the pathogenesis of fibrotic diseases and inhibition of which may represent a promising clinical approach for treating tissue fibrosis.
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Abstract Fibrosis is a common feature of fibrotic diseases that poses a serious threat to global health due to high morbidity and mortality in developing countries. There exist some chemical compounds and biomolecules associated w...
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Abstract Fibrosis is a common feature of fibrotic diseases that poses a serious threat to global health due to high morbidity and mortality in developing countries. There exist some chemical compounds and biomolecules associated with the development of fibrosis, including cytokines, hormones, and enzymes. Among them, glutathione peroxidase 4 (GPX4), as a selenoprotein antioxidant enzyme, is widely found in the embryo, testis, brain, liver, heart, and photoreceptor cells. Moreover, it is shown that GPX4 elicits diverse biological functions by suppressing phospholipid hydroperoxide at the expense of decreased glutathione (GSH), including loss of neurons, autophagy, cell repair, inflammation, ferroptosis, apoptosis, and oxidative stress. Interestingly, these processes are intimately related to the occurrence of fibrotic disease. Recently, GPX4 has been reported to exhibit a decline in fibrotic disease and inhibit fibrosis, suggesting that alterations of GPX4 can change the course or dictate the outcome of fibrotic disease. In this review, we summarize the role and underlying mechanisms of GPX4 in fibrosis diseases such as lung fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, and myelofibrosis.
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Circular RNAs (circRNAs) are a novel class of noncoding RNAs produced during pre-mRNA splicing and are emerging as new members of the gene regulatory network. Unlike linear RNAs, circRNAs have a unique structure with a covalently ...
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Circular RNAs (circRNAs) are a novel class of noncoding RNAs produced during pre-mRNA splicing and are emerging as new members of the gene regulatory network. Unlike linear RNAs, circRNAs have a unique structure with a covalently closed loop formed from the ligation of exons, introns, or both. CircRNAs are widely expressed in various organisms in a species-, tissue-, developmental stage- and disease-specific manner; circRNAs have been demonstrated to play a vital role in the pathogenesis and progression of human diseases. Fibrosis is characterized by an abnormal excessive deposition of extracellular matrix (ECM) in the extracellular space and plays important roles in many different pathologies of various organs. CircRNAs function as master regulators of gene expression to "sponge" or sequester other genes and target gene expression, transcription, splicing, etc. Increasing evidence has revealed that circRNAs are tightly associated with fibrotic diseases in various organs, including the lungs, liver, heart and kidneys. Herein, we provide the current understanding of the molecular characteristics of circRNAs and summarize the findings from circRNA studies in which the functions and mechanisms of action of circRNAs in organ fibrosis were proposed.
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ABSTRACT Post‐operative skeletal fibrosis is considered one of the major complications causing dysfunction of the skeletal system and compromising the outcomes of clinical treatment. Limited success has been achieved using curren...
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ABSTRACT Post‐operative skeletal fibrosis is considered one of the major complications causing dysfunction of the skeletal system and compromising the outcomes of clinical treatment. Limited success has been achieved using current therapies; more effective therapies to reduce post‐operative skeletal fibrosis are needed. Stem cells possess the ability to repair and regenerate damaged tissue. Numerous studies show that stem cells serve as a promising therapeutic approach for fibrotic diseases in tissues other than the skeletal system by inhibiting the inflammatory response and secreting favorable cytokines through activating specific signaling pathways, acting as so‐called medicinal signaling cells. In this review, current therapies are summarized for post‐operative skeletal fibrosis. Given that stem cells are used as a promising therapeutic approach for fibrotic diseases, little effort has been undertaken to use stem cells to prevent post‐operative skeletal fibrosis. This review aims at providing useful information for the potential application of stem cells in preventing post‐operative skeletal fibrosis in the near future. ? 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1236–1245, 2019.
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Objectives: An increasing percentage of cystic fibrosis (CF) diagnoses are occurring in adulthood.
The purpose of this study was to explore how age at diagnosis may be associated with selected
disease and sociodemographic characte...
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Objectives: An increasing percentage of cystic fibrosis (CF) diagnoses are occurring in adulthood.
The purpose of this study was to explore how age at diagnosis may be associated with selected
disease and sociodemographic characteristics.
Design: The 1996 Cystic Fibrosis Foundation (CFF) Patient Registry data were analyzed to test
for associations between age at diagnosis and selected variables. All cases involved individuals
> 18 years who were represented in the CFF Patient Registry for 1996. Patients were assigned
to one of two groups: those diagnosed with CF after age 18 years (n 5 786) and those diagnosed
before 18 years (n 5 6,641).
Results: In 1996, the incidence of late diagnosis was 7.8%, and the prevalence was 10.9%. The
mean age of late diagnosis was 27 years. Respiratory symptoms most frequently led to late
diagnosis. Patients receiving a late CF diagnosis were less likely to have alleles for Delta F508.
There was no correlation between age at diagnosis and percent predicted FEV1, although
patients in the late-diagnosis group were an average of 10 years older than those in the
early-diagnosis group. Late diagnosis was associated with fewer complications, fewer hospital-
izations, less oxygen use, fewer courses of home IV treatment, and less enzyme use. Women were
most often diagnosed late. Men displayed more diversity in conditions leading to diagnosis.
Psychosocially, those patients receiving late diagnoses were more likely to be college graduates,
married, and employed full time. For those adults who died in 1996, there was a positive
association between their age at diagnosis and age at death.
Conclusion: Those patients diagnosed with CF as adults differ, both medically and psychosocially,
from those diagnosed at a younger age; these differences have implications for diagnosis,
treatment, and education
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Fibrosis can affect almost every organ and represents an increasing cause of morbidity and mortality worldwide. Despite significant progress in our understanding of the pathobiology of fibrosis, there is still a lack of putative a...
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Fibrosis can affect almost every organ and represents an increasing cause of morbidity and mortality worldwide. Despite significant progress in our understanding of the pathobiology of fibrosis, there is still a lack of putative anti-fibrotic targets to be exploited in anti-fibrosis therapies or used as biomarkers of fibrosis progression. The discovery that HIPK2 can control molecular pathways involved in fibrosis has opened a new field of study in both pathophysiology and the treatment of fibrosis.
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Improved quality of care and rapidly emerging therapeutic strategies to restore chloride transport profoundly impact the epidemiology and pathobiology of cystic fibrosis (CF) in the twenty-first century. CF now serves as a model f...
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Improved quality of care and rapidly emerging therapeutic strategies to restore chloride transport profoundly impact the epidemiology and pathobiology of cystic fibrosis (CF) in the twenty-first century. CF now serves as a model for chronic illness management, continuous quality improvement via registry data, and a seamless link between basic science research, translational studies, clinical trials, and outcomes research to enable rapid expansion of treatment options.
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