scholarly journals Dipeptidylpeptidase 4 as a Marker of Activated Fibroblasts and a Potential Target for the Treatment of Fibrosis in Systemic Sclerosis

2019 ◽  
Vol 72 (1) ◽  
pp. 137-149 ◽  
Author(s):  
Alina Soare ◽  
Hermina A. Györfi ◽  
Alexandru E. Matei ◽  
Clara Dees ◽  
Simon Rauber ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Potential Target ◽  
Dipeptidylpeptidase 4 ◽  
Activated Fibroblasts

scholarly journals Sustained mechanical tension governs fibrogenic activation of tendon stromal cells in systemic sclerosis

2021 ◽  
Author(s):  
Amro A. Hussien ◽  
Robert Knell ◽  
Florian Renoux ◽  
Stefania Wunderli ◽  
Barbara Niederoest ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Tissue Mechanics ◽  
Matrix Stiffness ◽  
Stromal Fibroblasts ◽  
3D Matrix ◽  
Clinical Models ◽  
Function Relationship ◽  
Activated Fibroblasts ◽  
Tissue Models

Fibrosis is a pathological outcome of aberrant repair responses in systemic sclerosis and affects many tissues, including tendons. Progressive matrix stiffening is a key feature of this pathological remodeling. How dysregulated tissue mechanics contribute to the persistence of the fibrotic phenotype has been obscured by limited availability of experimental tissue models that are both controllable and capture essential aspects of the tendon biophysical niche. Here, we developed a modular, cantilever-based platform that allows culture of 3D tendon-like constructs under easily variable static tension, emulating this central tendon-specific structure function relationship. The system reveals that elevated matrix tension instigates fibroblast-to-myofibroblast activation eliciting scar-like phenotypes in vitro. By using this mechano-culture system and preclinical and clinical models of systemic sclerosis, we further show that 3D matrix stiffness is inversely correlated with the transcription of major pro-fibrotic collagens, but positively correlate with the expression of markers of stromal-immune interactions. Co-culture of tendon stromal fibroblasts and bone marrow-derived macrophages override stiffness-mediated downregulation of matrix transcription, suggesting that normal tension mediated checkpoints are superseded by the local tissue immune state. Our study highlights the power of 3D reductionist approaches in dissecting the contribution of the elevated matrix tension to the positive feedforward loops between activated fibroblasts and progressive ECM stiffening in systemic sclerosis.

Reactive oxygen species-mediated killing of activated fibroblasts by arsenic trioxide ameliorates fibrosis in a murine model of systemic sclerosis

2012 ◽  
Vol 64 (10) ◽  
pp. 3430-3440 ◽  
Author(s):  
Niloufar Kavian ◽  
Wioleta Marut ◽  
Amélie Servettaz ◽  
Carole Nicco ◽  
Christiane Chéreau ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Arsenic Trioxide ◽  
Murine Model ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Activated Fibroblasts

The IL1-like cytokine IL33 and its receptor ST2 are abnormally expressed in the affected skin and visceral organs of patients with systemic sclerosis

2009 ◽  
Vol 69 (3) ◽  
pp. 598-605 ◽  
Author(s):  
Mirko Manetti ◽  
Lidia Ibba-Manneschi ◽  
Vasiliki Liakouli ◽  
Serena Guiducci ◽  
Anna Franca Milia ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rt Pcr ◽  
Interleukin 33 ◽  
Pulmonary Fibroblasts ◽  
Confocal Immunofluorescence Microscopy ◽  
Confocal Immunofluorescence ◽  
Skin Biopsies ◽  
Activated Fibroblasts ◽  
St2 Receptor

BackgroundEarly endothelial cell (EC) activation/damage and profibrotic Th2-associated cytokines play a pivotal role in systemic sclerosis (SSc). Interleukin 33 (IL33) is a novel member of the IL1 family that promotes Th2 responses and inflammation through the ST2 receptor. IL33 is also a chromatin-associated transcriptional regulator in ECs.ObjectiveTo investigate the role of the IL33/ST2 axis in SSc.MethodsSkin biopsies were obtained from 30 patients with SSc (15 early/15 late stage) and 10 healthy subjects. Lung, kidney, heart, oesophagus, stomach, placenta biopsies and bronchoalveolar lavage cells from patients with SSc and controls were also analysed. IL33/ST2 expression was investigated by immunohistology, confocal immunofluorescence microscopy, western blotting and RT-PCR.ResultsIn skin biopsies from control subjects, constitutive nuclear IL33 protein expression was found in dermal ECs and keratinocytes, while ST2 was weakly expressed in ECs and fibroblasts. In skin biopsies from patients with early SSc, IL33 protein was downregulated or absent in ECs and epidermis while IL33 mRNA was normally expressed or even upregulated. Moreover, ECs, perivascular infiltrating mast cells, CD68-positive macrophages, CD3-positive T cells, CD20-positive B cells and activated fibroblasts/myofibroblasts exhibited strong ST2 expression. In skin biopsies from patients with late SSc, IL33 was constitutively found in most ECs while ST2 immunostaining was weaker. In early SSc, the loss of endothelial IL33 protein and the overexpression of ST2 involved all affected organs. Dermal and pulmonary fibroblasts showed IL33 expression in SSc.ConclusionIL33 and ST2 are abnormally expressed in SSc. In early SSc, upon EC activation/damage IL33 may be mobilised from ECs to signal through ST2 in key profibrotic players such as inflammatory/immune cells and fibroblasts/myofibroblasts.

scholarly journals Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis

2009 ◽  
Vol 60 (5) ◽  
pp. 1519-1529 ◽  
Author(s):  
Hossein Hemmatazad ◽  
Hanna Maciejewska Rodrigues ◽  
Britta Maurer ◽  
Fabia Brentano ◽  
Margarita Pileckyte ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Histone Deacetylase ◽  
Potential Target
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