scholarly journals Involvement of αvβ5 integrin-mediated activation of latent transforming growth factor β1 in autocrine transforming growth factor β signaling in systemic sclerosis fibroblasts

2005 ◽  
Vol 52 (9) ◽  
pp. 2897-2905 ◽  
Author(s):  
Yoshihde Asano ◽  
Hironobu Ihn ◽  
Kenichi Yamane ◽  
Masatoshi Jinnin ◽  
Yoshihiro Mimura ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1

Increased aortic stiffness in the insulin-resistant Zucker fa/fa rat

2005 ◽  
Vol 289 (2) ◽  
pp. H845-H851 ◽  
Author(s):  
Akhilesh K. Sista ◽  
Mary K. O'Connell ◽  
Tomoya Hinohara ◽  
Santosh S. Oommen ◽  
Brett E. Fenster ◽  
...  
Keyword(s):  
Growth Factor ◽  
Aortic Stiffness ◽  
Transforming Growth Factor ◽  
Longitudinal Direction ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Vascular Stiffness ◽  
Molecular Evidence ◽  
Mechanical Stiffness ◽  
Insulin Resistant

Accumulating clinical evidence indicates increased aortic stiffness, an independent risk factor for cardiovascular and all-cause mortality, in type 2 diabetic and glucose-intolerant individuals. The present study sought to determine whether increased mechanical stiffness, an altered extracellular matrix, and a profibrotic gene expression profile could be observed in the aorta of the insulin-resistant Zucker fa/fa rat. Mechanical testing of Zucker fa/fa aortas showed increased vascular stiffness in longitudinal and circumferential directions compared with Zucker lean controls. Unequal elevations in developed strain favoring the longitudinal direction resulted in a loss of anisotropy. Real-time quantitative PCR and immunohistochemistry revealed increased expression of fibronectin and collagen IVα3 in the Zucker fa/fa aorta. In addition, expression of transforming growth factor-β and several Smad proteins was increased in vessels from insulin-resistant animals. In rat vascular smooth muscle cells, 12–18 h of exposure to insulin (100 nmol/l) enhanced transforming growth factor-β1 mRNA expression, implicating a role for hyperinsulinemia in vascular stiffness. Thus there is mechanical, structural, and molecular evidence of arteriosclerosis in the Zucker fa/fa rat at the glucose-intolerant, hyperinsulinemic stage.

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.

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