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Terpenoids: The Biological Key Molecules
Published in Dijendra Nath Roy, Terpenoids Against Human Diseases, 2019
Moumita Majumdar, Dijendra Nath Roy
The transforming growth factor β (TGF-β) superfamily comprises numerous growth factors—including, for example, TGF-β-1,2,3 and bone morphogenetic proteins—by which they regulate physiological processes such as cell differentiation, development, proliferation, adhesion, movement and, ultimately, programmed cell death. Cytokines of the TGF-β superfamily accelerate heterotetrameric receptor complex formation. These structures are composed of mainly two transmembrane receptor proteins, namely TGF-β receptor I (TβRI) and TGF-β receptor II (TβRII). Phosphorylation of these receptors results in the activation of a downstream transcription factor, which in turn phosphorylates SMAD2 and SMAD3. TGF-β receptor 1 phosphorylates R-SMADs on their C terminus through the intracellular kinase domain, leading to R-SMAD activation (Wharton and Derynck 2009). Then, R-SMADs interact with SMAD4 to form a SMAD complex, leading to its translocation to the nucleus for gene expression. On the other hand, bone morphogenetic proteins activate SMADl, SMAD5 and SMAD8.
Thioredoxin-Based Peptide Aptamers: Development and Applications
Published in Rakesh N. Veedu, Aptamers, 2017
David S. Burz, Sergey Reverdatto, Alexander Shekhtman
Cui et al. [68] employed rational design to introduce PAs derived from the interaction motifs of Smad-binding proteins CBP (49 amino acids), FoxH1 (24 amino acids), and Lef1 (tandem duplication of 30 amino acids) into the TrxA scaffold to inhibit transforming growth factor beta (TGF-β)-induced gene expression. TGF-β alters gene expression by activating type I serine kinase receptors, which, in turn, phosphorylate Smad2 and Smad 3. Smad2 and Smad 3 form heterooligomeric complexes with Smad4 that accumulate in the nucleus and bind > 20 nuclear transcription factors, including CBP, FoxH1, and Lef1. These specific interactions give rise to the cell-type-specific effects of stimulating TGF-β gene expression, such as proliferation, apoptosis, and differentiation. The three PAs examined bind specifically to Smads and differentially inhibit TGF-β-induced gene expression in HepG2 cells.
Role of Krüppel-Like Factors in Endothelial Cell Function and Shear Stress–Mediated Vasoprotection
Published in Juhyun Lee, Sharon Gerecht, Hanjoong Jo, Tzung Hsiai, Modern Mechanobiology, 2021
Transforming growth factor-ß (TGF-ß) has been proposed to regulate endothelial cell activation [72]. KLF2 regulates the TGF-ß-mediated proinflammatory response in endothelial cells by inducing Smad7, a potent attenuator of TGF-ß signaling. This results in a reduction of the phosphorylation and nuclear accumulation of Smad2 and the Smad3/4-dependent transcriptional cascade, thereby abrogating TGF-ß signaling. Furthermore, it was demonstrated that KLF2 can inhibit AP-1, an important cofactor in TGF-p-mediated
Devices for penile traction: the long and winding road to treating Peyronie’s disease
Published in Expert Review of Medical Devices, 2018
Shaan A Setia, Laurence A Levine
An important study by Chung et al. in 2012 showed the consequences of applying prolonged mechanical stress to tunical tissue. In this study, a pressurized chamber system applied hydrostatic pressure to cellular cultures of PD and normal tunical tissue. They found increased MMPs, most significantly MMP-8, in the strained PD tissues compared to the normal tissue. This indicated that the PD tunical tissue is likely to respond to mechanical strain and promote collagen degradation [21]. Molecular changes were also confirmed in a rat model. In this study, penile tunical scarring was induced following TGF-beta injection in 30 rats which were randomized into control, traction device, and vacuum device arms. They found that both the traction device group and vacuum erection device (VED) group had decreased penile curvature compared to control. Additionally, immunohistochemistry showed that the VED group had more preserved alpha-smooth muscle actin and less TGF-beta in the corpus cavernosa compared to both other groups [22]. This suggested that the mechanism of PTT involves antifibrosis and smooth muscle preservation. In a similar study by Li Jinhong et al., rats with induced tunical scarring from TGF-beta injection underwent VED therapy. Six weeks after injection, there was a significant increase in TGF‐beta, SMAD2, SMAD3, and p‐SMAD2/3 protein expression in both groups. The expression of these proteins, however, decreased after VED therapy [23].