scholarly journals The Histone Deacetylase Sirtuin 1 Is Reduced in Systemic Sclerosis and Abrogates Fibrotic Responses by Targeting Transforming Growth Factor β Signaling

2015 ◽  
Vol 67 (5) ◽  
pp. 1323-1334 ◽  
Author(s):  
Jun Wei ◽  
Archit K. Ghosh ◽  
Haiyan Chu ◽  
Feng Fang ◽  
Monique E. Hinchcliff ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Histone Deacetylase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Sirtuin 1

scholarly journals Expression of transforming growth factor β receptor II in mesenchymal stem cells from systemic sclerosis patients

BMJ Open ◽  
2013 ◽  
Vol 3 (1) ◽  
pp. e001890 ◽  
Author(s):  
Valérie Vanneaux ◽  
Dominique Farge-Bancel ◽  
Séverine Lecourt ◽  
Julie Baraut ◽  
Audrey Cras ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Systemic Sclerosis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Β Receptor

scholarly journals Proteomic Analysis of Sera from Individuals with Diffuse Cutaneous Systemic Sclerosis Reveals a Multianalyte Signature Associated with Clinical Improvement during Imatinib Mesylate Treatment

2017 ◽  
Vol 44 (5) ◽  
pp. 631-638 ◽  
Author(s):  
D. James Haddon ◽  
Hannah E. Wand ◽  
Justin A. Jarrell ◽  
Robert F. Spiera ◽  
Paul J. Utz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Systemic Sclerosis ◽  
Growth Factor ◽  
Clinical Improvement ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Transforming Growth Factor Β ◽  
Elastic Net ◽  
Open Label ◽  
Link Type

Objective.Imatinib has been investigated for the treatment of systemic sclerosis (SSc) because of its ability to inhibit the platelet-derived growth factor receptor and transforming growth factor-β signaling pathways, which have been implicated in SSc pathogenesis. In a 12-month open-label clinical trial assessing the safety and efficacy of imatinib in the treatment of diffuse cutaneous SSc (dcSSc), significant improvements in skin thickening were observed. Here, we report our analysis of sera collected during the clinical trial.Methods.We measured the levels of 46 cytokines, chemokines, and growth factors in the sera of individuals with dcSSc using Luminex and ELISA. Autoantigen microarrays were used to measure immunoglobulin G reactivity to 28 autoantigens. Elastic net regularization was used to identify a signature that was predictive of clinical improvement (reduction in the modified Rodnan skin score ≥ 5) during treatment with imatinib. The signature was also tested using sera from a clinical trial of nilotinib, a tyrosine kinase inhibitor that is structurally related to imatinib, in dcSSc.Results.The elastic net algorithm identified a signature, based on levels of CD40 ligand, chemokine (C-X-C motif) ligand 4 (CXCL4), and anti-PM/Scl-100, that was significantly higher in individuals who experienced clinical improvement than in those who did not (p = 0.0011). The signature was validated using samples from a clinical trial of nilotinib.Conclusion.Identification of patients with SSc with the greatest probability of benefit from treatment with imatinib has the potential to guide individualized treatment. Validation of the signature will require testing in randomized, placebo-controlled studies. Clinicaltrials.govNCT00555581 and NCT01166139.

scholarly journals Transforming growth factor- β -induced CUX1 isoforms are associated with fibrosis in systemic sclerosis lung fibroblasts

2016 ◽  
Vol 7 ◽  
pp. 246-252 ◽  
Author(s):  
Tetsurou Ikeda ◽  
Maria Fragiadaki ◽  
Xu Shi-wen ◽  
Markella Ponticos ◽  
Korsa Khan ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Lung Fibroblasts

scholarly journals E2F and Histone Deacetylase Mediate Transforming Growth Factor β Repression of cdc25A during Keratinocyte Cell Cycle Arrest

1999 ◽  
Vol 19 (1) ◽  
pp. 916-922 ◽  
Author(s):  
Antonio Iavarone ◽  
Joan Massagué
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Arrest ◽  
Histone Deacetylase ◽  
Transforming Growth Factor ◽  
Human Keratinocytes ◽  
Transforming Growth Factor Β ◽  
Quiescent State ◽  
Cycle Arrest ◽  
Initial Drop

ABSTRACT cdc25A is a tyrosine phosphatase that activates G1cyclin-dependent kinases (Cdk’s). In human keratinocytes,cdc25A expression is down-regulated after the initial drop in Cdk activity caused by cell exposure to the antimitogenic cytokine transforming growth factor β (TGF-β) or removal of serum factors. Here we show that the TGF-β-inhibitory-response element in thecdc25A promoter maps to an E2F site at nucleotides −62 to −55 from the transcription start site. This site is not required for basal transcription in keratinocytes. We provide evidence that the cell cycle arrest program activated by TGF-β in human keratinocytes includes the generation of E2F4-p130 complexes that in association with histone deacetylase HDAC1 inhibit the activity of thecdc25A promoter from this repressor E2F site. This mechanism is part of a program that places keratinocytes in the quiescent state following the initial drop in Cdk activity caused by cell exposure to TGF-β.

scholarly journals JAK-2 as a novel mediator of the profibrotic effects of transforming growth factor β in systemic sclerosis

2012 ◽  
Vol 64 (9) ◽  
pp. 3006-3015 ◽  
Author(s):  
Clara Dees ◽  
Michal Tomcik ◽  
Katrin Palumbo-Zerr ◽  
Alfiya Distler ◽  
Christian Beyer ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β
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