Mediators of fibrosis.
Authors: Trojanowska M
PMID: 22802903 [PubMed] (Source: Open Rheumatology Journal)
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
New insights into the mechanisms of innate immune receptor signalling in fibrosis.
Authors: Lafyatis R, Farina A
Abstract
Recent advances in our understanding of innate immunity and inflammation have direct bearing on how we understand autoimmunity, and fibrosis, and how innate immune sensors might stimulate both of these key features of several fibrotic diseases. Toll-like receptors (TLRs) are the major receptors for recognizing pathogen associated molecular patterns present on bacterial cell walls, such as LPS, and nucleic acids (RNA and DNA). Several intracellular pathways mediate TLR effects and initiate various pro-inflammatory programs. Mechanisms for control of inflammation, matri...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
The Role of the NLRP3 Inflammasome in Fibrosis.
Authors: Artlett CM
Abstract
Fibrosis leads to the deposition of collagens in organs and tissues. The resulting pathology induces a loss of function in the organ it is manifested in and this loss of function modulates the morbidity and mortality in that individual. Indeed, approximately 45% of all deaths in the Western world can be attributed to fibrosis and there are no FDA approved drugs for the treatment of fibrosis. The recent discovery of the inflammasome has led to a plethora of studies investigating this inflammatory signaling pathway in a wide variety of pathogen associated diseases. Many studies h...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
New insights into the role of oxidative stress in scleroderma fibrosis.
Authors: Gabrielli A, Svegliati S, Moroncini G, Amico D
Abstract
Systemic sclerosis (Scleroderma - SSc) is a connective tissue disorder of unknown aetiology characterized by extensive fibrosis of the skin and visceral organs, by vascular abnormalities and immunological manifestations.Recent evidence suggest that the cellular redox state may play a significant role in the progression of scleroderma fibrosis. Mechanisms involved include an autoamplification circuit linking ROS, Ras and ERK 1-2 which in turn amplifies and maintains the autocrine loop made up by cytokines, growth factors and their cognate rece...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
New insights into the mechanism of notch signalling in fibrosis.
Authors: Kavian N, Servettaz A, Weill B, Batteux F
Abstract
The Notch pathway is an evolutionary conserved signalling mechanism that regulates cellular fate and development in various types of cells. The full spectrum of Notch effects has been well studied over the last decade in the fields of development and embryogenesis. But only recently several studies emphasized the involvement of the Notch signalling pathway in fibrosis. This review summarizes the structure and activation of the Notch family members, and focuses on recent findings regarding the role of Notch in organ fibrogenesis, in humans and in a...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
Regulation of Matrix Remodeling by Peroxisome Proliferator-Activated Receptor-γ: A Novel Link Between Metabolism and Fibrogenesis.
This article highlights recent studies revealing a consistent association of fibrosis with aberrant PPAR-γ expression and activity in various forms of human fibrosis and in rodent models, and reviews studies linking genetic manipulation of the PPAR-γ pathway in rodents and fibrosis. We survey the broad range of anti-fibrotic activities associated with PPAR-γ and the underlying mechanisms. We also summarize the emerging data linking PPAR-γ dysfunction and pulmonary arterial hypertension (PAH), which together with fibrosis is responsible for the mortality in patients in SSc. Finally, we consider current and potential fut...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
Caveolin-1 signaling in lung fibrosis.
Authors: Tourkina E, Hoffman S
Abstract
Caveolin-1 is a master regulator of several signaling cascades because it is able to bind to and thereby inhibit members of a variety of kinase families. While associated with caveolae and involved in their generation, caveolin-1 is also present at other sites. A variety of studies have suggested that caveolin-1 may be a useful therapeutic target in fibrotic diseases of the lung and other tissues because in these diseases a low level of caveolin-1 expression is associated with a high level of collagen expression and fibrosis. Reduced caveolin-1 expression is observed...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
Sphingolipid regulation of tissue fibrosis.
Authors: Shea BS, Tager AM
Abstract
Bioactive sphingolipids, such as sphingosine 1-phosphate (S1P), dihydrosphingosine 1-phosphate (dhS1P) and ceramide, regulate a diverse array of cellular processes. Many of these processes are important components of wound-healing responses to tissue injury, including cellular apoptosis, vascular leak, fibroblast migration, and TGF-β signaling. Since over-exuberant or aberrant wound-healing responses to repetitive injury have been implicated in the pathogenesis of tissue fibrosis, these signaling sphingolipids have the potential to influence the development and progress...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
Role of MicroRNAs in Fibrosis.
Authors: Vettori S, Gay S, Distler O
Abstract
Fibrosis is the leading cause of organ dysfunction in diseases such as systemic sclerosis, liver cirrhosis, cardiac fibrosis, progressive kidney disease, and idiopathic pulmonary fibrosis. The hallmark of fibrosis is tissue remodeling with excess deposition of extracellular matrix components, predominantly collagens. Different cell types, cytokines, growth factors, and enzymes interact in complex pathogenic networks with myofibroblasts playing a pivotal role. MicroRNAs are small non-coding RNAs acting as negative regulators of gene expression at the post-transc...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
Insulin-like growth factor binding proteins-3 and -5: central mediators of fibrosis and promising new therapeutic targets.
Authors: Veraldi KL, Feghali-Bostwick CA
Abstract
Fibrosis involves an orchestrated cascade of events including activation of fibroblasts, increased production and deposition of extracellular matrix components, and differentiation of fibroblasts into myofibroblasts. Epithelial-mesenchymal cross-talk plays an important role in this process, and current hypotheses of organ fibrosis liken it to an aberrant wound healing response in which epithelial-mesenchymal transition (EMT) and cellular senescence may also contribute to disease pathogenesis. The fibrotic response is associated with altered expression of gr...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
The Function of SPARC as a Mediator of Fibrosis.
Authors: Trombetta-Esilva J, Bradshaw AD
Abstract
Fibrosis is a common end-point of a number of different diseases such as hypertension, diabetes, liver cirrhosis, and those associated with chronic inflammation. Fibrosis is characterized by excessive deposition of extracellular matrix that interferes with normal tissue architecture and function. Increased expression of secreted protein acidic and rich in cysteine (SPARC) in fibrotic tissues has been reported in numerous studies. SPARC is a 43 kDa collagen-binding protein secreted from several different cell types into the extracellular matrix and has been ...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
The Role of TGF-β Receptors in Fibrosis.
Authors: Nakerakanti S, Trojanowska M
Abstract
Recent advances in defining TGF-β signaling pathways have provided a new level of understanding of the role of this pleiotropic growth factor in the development of fibrosis. Here, we review selected topics related to the profibrotic role of TGF-β . We will discuss new insights into the mechanisms of ligand activation and the contribution of Erk1/2 MAPK, PI3K/FAK, and Endoglin/Smad1 signaling pathways to the process of fibrosis. There is growing evidence of the disease-specific alterations of the downstream components of the TGF-β signaling pathway that may ...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
Getting out of a sticky situation: targeting the myofibroblast in scleroderma.
Authors: Leask A
Abstract
There is no treatment for the fibrosis observed in scleroderma (systemic sclerosis, SSc). Although genome-wide expression profiling has suggested that differences in gene expression patters between non-lesional and lesional skin are minimal, phenotypically these areas of tissue are quite different. In fact, lesional areas of scleroderma patients can be distinguished by the presence of a differentiated form of fibroblast, termed the myofibroblast. This cell type expresses the highly contractile protein α-smooth muscle actin (α-SMA). Fibroblasts isolated from SSc lesions excessive...
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
Sicca Symptoms and their Association with Chronic Rhinosinusitis in a Community Sample.
CONCLUSIONS: Sicca symptoms are common in the community. Our novel finding of a strong association between dry eyes and CRS suggests that further research into the relationship between airway inflammation and sicca symptoms is required. These findings may have particular relevance to Sjögren's syndrome (SS) in both its primary and secondary forms.
PMID: 22802916 [PubMed] (Source: Open Rheumatology Journal)
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
Delayed Positivization of Cerebral Angiography in Reversible Cerebral Vasoconstriction Syndrome (RCVS) Presenting with Recurrent Subarachnoid Haemorrhage.
We describe a case of RCVS presenting with a subarachnoid haemorrhage (SAH), with rebleeding and onset of hydrocephalus during the first week, and, notably, delayed evidence of typical angiographic features after two negative prior exams. Normalization of the angiographic vasculitic-like lesions was documented at month +6. Repeated cerebral angiograms are mandatory to exclude this kind of disease, and the uncommon presentation of this case reinforces this concept.
PMID: 22870164 [PubMed] (Source: Open Rheumatology Journal)
Source: Open Rheumatology Journal - December 2, 2014 Category: Rheumatology Tags: Open Rheumatol J Source Type: research
