scholarly journals The integrin alphavbeta3 is a receptor for the latency-associated peptides of transforming growth factors beta1 and beta3

2003 ◽  
Vol 369 (2) ◽  
pp. 311-318 ◽  
Author(s):  
Steven B. LUDBROOK ◽  
Simon T. BARRY ◽  
Chris J. DELVES ◽  
Carmel M.T. HORGAN
Keyword(s):  
Transforming Growth Factor ◽  
Integrin Αvβ3 ◽  
Transforming Growth Factor Β1 ◽  
Glutathione S Transferase ◽  
Binding Properties ◽  
Rgd Motif ◽  
Integrin Alphavbeta3 ◽  
Molecule Inhibitor ◽  
Fibrotic Diseases ◽  
Binding Loop

The integrins αvβ1, αvβ5, αvβ6 and αvβ8 have all recently been shown to interact with the RGD motif of the latency-associated peptide (LAPβ1) of transforming growth factor β1 (TGFβ1), with binding to αvβ6 and αvβ8 leading to TGFβ1 activation. Previously it has been suggested that the remaining αv integrin, αvβ3, does not interact with LAPβ1. However, here we show clearly that αvβ3 does indeed interact with the LAPβ1 RGD motif. This interaction is similar to other αvβ3 ligands in terms of the cations required for adhesion, the concentrations of LAPβ1 required for binding and the ability of a small-molecule inhibitor of αvβ3, SB223245, to block the interaction. Using glutathione S-transferase fusion proteins we have mapped a minimal integrin-binding loop in LAPβ1 and then used this approach to probe the integrin-binding properties of the equivalent loops in LAPβ2 and LAPβ3. We show that the RGD motif of LAPβ3 also interacts with αvβ3, in addition to αvβ6, αvβ1 and αvβ5, whereas the corresponding loop in LAPβ2 does not interact with these integrins. These observations therefore correct a previously reported inaccuracy in the literature. Furthermore, they are important as they link αvβ3 and TGFβ, which may have implications in cancer and a number of inflammatory and fibrotic diseases where expression of both proteins has been documented.

scholarly journals Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix

2007 ◽  
Vol 179 (6) ◽  
pp. 1311-1323 ◽  
Author(s):  
Pierre-Jean Wipff ◽  
Daniel B. Rifkin ◽  
Jean-Jacques Meister ◽  
Boris Hinz
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Mechanical Stress ◽  
Protease Activity ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Stress Fibers ◽  
Fibrotic Diseases ◽  
Triton X ◽  
Tgf Β1

The conjunctive presence of mechanical stress and active transforming growth factor β1 (TGF-β1) is essential to convert fibroblasts into contractile myofibroblasts, which cause tissue contractures in fibrotic diseases. Using cultured myofibroblasts and conditions that permit tension modulation on the extracellular matrix (ECM), we establish that myofibroblast contraction functions as a mechanism to directly activate TGF-β1 from self-generated stores in the ECM. Contraction of myofibroblasts and myofibroblast cytoskeletons prepared with Triton X-100 releases active TGF-β1 from the ECM. This process is inhibited either by antagonizing integrins or reducing ECM compliance and is independent from protease activity. Stretching myofibroblast-derived ECM in the presence of mechanically apposing stress fibers immediately activates latent TGF-β1. In myofibroblast-populated wounds, activation of the downstream targets of TGF-β1 signaling Smad2/3 is higher in stressed compared to relaxed tissues despite similar levels of total TGF-β1 and its receptor. We propose activation of TGF-β1 via integrin-mediated myofibroblast contraction as a potential checkpoint in the progression of fibrosis, restricting autocrine generation of myofibroblasts to a stiffened ECM.

scholarly journals The Potential Protective Effect of Oligoribonucleotides-d-Mannitol Complexes against Thioacetamide-Induced Hepatotoxicity in Mice

2018 ◽  
Vol 11 (3) ◽  
pp. 77 ◽  
Author(s):  
Tetiana Marchyshak ◽  
Tetiana Yakovenko ◽  
Igor Shmarakov ◽  
Zenoviy Tkachuk
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Transforming Growth Factor ◽  
Elevated Serum ◽  
Transforming Growth Factor Β1 ◽  
Hepatoprotective Activity ◽  
Protein Carbonyl ◽  
Glutathione S Transferase ◽  
Sh Group ◽  
Factor Α

This study investigated the potential hepatoprotective effect of oligoribonucleotides-d-mannitol complexes (ORNs-d-M) against thioacetamide (TAA)-induced hepatotoxicity in mice. The hepatoprotective activity of ORNs-d-M was evaluated in thioacetamide (TAA)-treated C57BL/6J. Results indicate that treatment with ORNs-d-M displayed a protective effect at the TAA-induced liver injury. Treatment with ORNs-d-M, starting at 0 h after the administration of TAA, decreased TAA-elevated serum alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT). Activities of glutathione S-transferase (GST) and glutathione peroxidase (GPx), and levels of glutathione (GSH), were enhanced with ORNs-d-M administration, while the hepatic oxidative biomarkers (TBA-reactive substances, protein carbonyl derivatives, protein-SH group) and myeloperoxidase (MPO) activity were reduced. Furthermore, genetic analysis has shown that the ORNs-d-M decreases the expression of mRNA pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), profibrogenic cytokine-transforming growth factor β1 (TGF-β1), as well as the principal protein of the extracellular matrix—collagen I. The present study demonstrates that ORNs-d-M exerts a protective effect against TAA-induced liver injury, which may be associated with its anti-inflammatory effects, inhibition of overexpression of mRNA cytokines, and direct effects on the metabolism of the toxin.

scholarly journals Glutathione S-Transferase Omega-2 and Transforming Growth Factor-β1 Polymorphisms in Iranian Glaucoma Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Shahram Bamdad ◽  
Fatemeh Sanie-Jahromi ◽  
Marzieh Alamolhoda ◽  
Nasrin Masihpour ◽  
Mohammad-Hossein Karimi
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Open Angle Glaucoma ◽  
Transforming Growth Factor Β1 ◽  
Angle Closure ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Significant Difference ◽  
And Control ◽  
Tgf Β1

Background. To investigate the association of glutathione s-transferase omega 2 (GSTO2) (142N > D) and transforming growth factor-β1 (TGF-β1) (869T > C) gene polymorphisms on the pathogenesis of two common types of glaucoma (including primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG)) in the Iranian population. Methods. A total of 100 glaucoma patients (60% males and 40% females with an age mean ± SD of 34.66 ± 14.25 years; 56 cases of POAG and 44 cases of CACG) were enrolled in this study. GSTO2 (142N > D) and TGF-β1 (869T > C) polymorphisms were evaluated by PCR-based methods in patients and controls. Results. At locus GSTO2 (142N > D), the odds of ND genotype with respect to DD and NN genotypes were 1.55 and 2.08 times higher in POAG and CACG patients compared to those of patients in the control group (95% CI1: 0.80–2.98; 95% CI2: 1.00–4.33) which was statistically significant in CACG patients. However, the odds of DD and NN genotypes against the reference genotype in two patients group were not statistically significant as compared to those of patients in the control group. There was a significant association between the ND genotype and male patients (OR = 2.28, 95% CI: 1.06–4.92). The analysis of TGF-β1 (869T > C) polymorphisms showed no significant difference between the genotypes of TGF-β1 (869T > C) polymorphisms in patients and control groups; however, the CT genotype of TGF-β1 significantly differed between female controls and patients (OR = 0.42, 95% CI: 0.18–0.96). Conclusion. The presented results revealed that there was a significant association between the ND genotype of GSTO2 and the pathogenesis of glaucoma. Furthermore, this genotype can be considered as a sex-dependent genetic risk factor for the development of glaucoma. In contrast, the CT genotype of TGF-β1 is suggested to be a protective genetic factor against the pathogenesis of glaucoma.

scholarly journals Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1

2021 ◽  
Vol 15 ◽  
pp. 175346662098185
Author(s):  
Rujie Huo ◽  
Xinli Tian ◽  
Qin Chang ◽  
Dai Liu ◽  
Chen Wang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Cell Model ◽  
Airway Remodeling ◽  
Transforming Growth Factor Β1 ◽  
Mesenchymal Transition ◽  
Molecule Inhibitor ◽  
Anti Inflammatory ◽  
Targeted Inhibition

Background: TGF-β1 is a key cytokine involved in both airway inflammation and airway remodeling in asthma because of its anti-inflammatory and profibrotic effect. In our previous study, we found that knockdown of cytosolic β-catenin alleviated the profibrogenic effect of TGF-β1 without influencing its anti-inflammatory effect. However, the exact role of targeting β-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting β-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. Methods: We integrated experimental asthma model and asthma related cell model to explore the effect of targeting β-catenin on airway inflammation and remodeling of asthma. Results: Blocking β-catenin with ICG001, a small molecule inhibitor of β-catenin/TCF via binding to cAMP-response elementbinding protein, attenuated airway inflammation by increasing levels of anti-inflammation cytokines IL-10, IL-35 and decreasing levels of T helper (Th)2 cells and Th17 cytokine. Suppressing β-catenin by ICG001 inhibited airway remodeling via reducing the level of TGF-β1 and the expressions of Snail, MMP-7, MMP-9 and, up-regulating expression of E-cadherin, down-regulating expressions of α-SMA and Fn. Inhibition of β-catenin with ICG001 suppressed TGF-β1 induced proliferation and activation of CCC-REPF-1, blocked TGF-β1 induced epithelial–mesenchymal transition (EMT) of RLE-6TN. Conclusion: Blockade of β-catenin/TCF not only prevents TGF-β1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing pro-inflammatory and anti-inflammatory cytokine. In conclusion, targeting β-catenin specifically via inhibition of β-catenin/TCF might be a new therapeutic strategy for asthma. The reviews of this paper are available via the supplemental material section.

583: Transforming Growth Factor β1 and its Receptors are Related to the Development, Recurrence and Prgression of Human Bladder Cancers

2005 ◽  
Vol 173 (4S) ◽  
pp. 159-159
Author(s):  
Wun-Jae Kim ◽  
ChangYi Quan ◽  
Pil-Du Jeoung ◽  
Eun-Jung Kim ◽  
Ji-Yeon Kim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Human Bladder
Sign in / Sign up

Export Citation Format

Share Document