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Bone Regeneration Effect of Cassia occidentalis Linn. Extract and Its Isolated Compounds
Published in Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay, Phytochemistry of Plants of Genus Cassia, 2021
Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay
Induction of osteoblast differentiation by emodin is associated with the upregulation of BMP-9, osterix, activin receptor-like kinase 1 (ALK1), smad 1, smad 9 and Msh homeobox 2 (Msx2) mRNA levels in osteoblasts. Emodin-induced osteogenic differentiation could be blocked by noggin, thus suggesting the role of BMP-9 as the mediator of this process as BMP-2 expression was unchanged by emodin. In OVX rats, emodin (100 mg/kg, route of administration unspecified) given for 12 weeks although inhibited tartrate-resistant acid phosphatase 5b (TRACP5b, the surrogate of osteoclast number) had no effect on preventing loss of bone volume and strength. A “low dose” E2 (50 μg/kg) also had no effect however, when combined with emodin, complete protection against OVX-induced trabecular osteopenia and loss of strength was observed. As 50 μg/kg E2 had no uterotrophic effect, a combination of low-dose E2 and emodin has been suggested for the treatment of postmenopausal osteoporosis (Chen et al., 2017).
Participation of Cytokines and Growth Factors in Biliary Epithelial Proliferation and Mito-Inhibition during Ductular Reactions
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Anthony J. Demetris, J.G. Lunz, Vladimir Subbotin, Tong Wu, Isao Nozaki, Sarah Contrucci, Xia Yin
The active form of TGF (beta) binds to the TGFβ receptor II (TβR-II), which dimerizes with and phosphorylates TGF(beta) receptor I (TβR-I). Similarly, activin A binds to the activin receptor II, which dimerizes with activin receptor I. Signal transduction by either of these family members (Fig. 5) is perpetuated by receptor complex phosphorylation of a receptor-regulated SMAD protein (SMAD2 or 3), followed by heterodimerization of the receptor-regulated SMAD with a coSMAD (SMAD4). This complex can then enter the nucleus, where it can interact with a DNA binding partner (DBP) to influence gene transcription. TGF(beta) family members can stimulate transcription of growth inhibitory genes such as p21, or inhibit transcription of growth promoting genes, such as c-myc.165
TGF-β signaling in testicular development, spermatogenesis, and infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Poonam Mehta, Meghali Joshi, Rajender Singh
The mechanism of action of activin involves its binding to one of the type II activin receptors (ACVR2A or ACVR2B) present on the target cell, ligand-receptor interaction, receptor dimerization which brings the type I receptor closer to the type II receptor. Binding of type I receptor to type II induces phosphorylation of the type I receptor, which in turn induces phosphorylation of intracellular and cytosolic proteins SMAD2 and SMAD3. These proteins along with Co-SMAD4 form a transcription activation complex, which on translocation to the nucleus regulates proliferation, differentiation and apoptotic genes (53).
Pharmacotherapeutic options for cancer cachexia: emerging drugs and recent approvals
Published in Expert Opinion on Pharmacotherapy, 2023
Lorena Garcia-Castillo, Giacomo Rubini, Paola Costelli
Anti-Activin Receptor IIB approaches, including those targeting myostatin, have received quite a lot of attention due to the ability of the underlying signal transduction pathway to work as a negative regulator of muscle mass [56]. In this regard, few trials were performed using anti-myostatin tools such as the monoclonal antibody LY2495655 and the AMG745/Mu-S peptibody. While the latter proved effective in improving lean body mass in prostate cancer patients [57], the former failed to confirm such expectations. Indeed, the trial was interrupted due to significant side effects, in the absence of an appreciable clinical benefit [58]. Finally, a phase II clinical trial (ClinicalTrials.gov Identifier: NCT01433263) tested the effectiveness of Bimagrumab, an anti-Activin Receptor in patients affected by advanced lung or pancreatic cancer, showing improved lean body mass. Despite such controversial results, targeting the Activin Receptor II-dependent pathway remains an attractive option that deserves further investigation.
An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment
Published in Hemoglobin, 2023
Mohammadreza Saeidnia, Pooria Fazeli, Arghavan Farzi, Maryam Atefy Nezhad, Mojtaba Shabani-Borujeni, Mehran Erfani, Gholamhossein Tamaddon, Mehran Karimi
Activin II receptor traps are included in Luspatercept, and Sotatercept are suitable for NTDT patients’ treatment. GDF-11 is an activin that is a member of transforming growth factor-β (TGF-β) cluster that acts as an effective molecule in erythropoiesis. Activin receptors are composed of activin type IIA receptor (ARIIA) and activin type IIB receptor (ARIIB) [94]. Interaction of GDF-11 with one of the receptors causes stimulation of activin type I receptor recruitment and triggers phosphorylation cascade from activin type I receptor to Smad2 and Smad3. As GDF-11 plays a pivotal role in modulating last-stage of erythroid precursor proliferation, maturation, and differentiation mediated by GDF-11-ARIIB-Smad2/3 signal transduction pathway, the mechanism of activin II receptor traps is based on ligands blocking, which includes Luspatercept (ACE-536/REBLOZYL) and Sotatercept (ACE-011) [94,97].
Differential expression of BMP/SMAD signaling and ovarian-associated genes in the granulosa cells of FecB introgressed GMM sheep
Published in Systems Biology in Reproductive Medicine, 2020
Satish Kumar, Pradeep Kumar Rajput, Sangharatna V. Bahire, Basanti Jyotsana, Vijay Kumar, Davendra Kumar
It is well known that the BMP factors (ligands) act through the two sub-types of receptors with serine/threonine kinase activity. Seven type I receptors and five type II serine/threonine kinase receptors have been reported (Attisano and Wrana 1996). Activin receptor-like kinase 1 (Alk1 or ACVRL1), Alk2 (ACVR1), Alk3 (BMPR1A), Alk4 (ACVR1B), Alk5 (TGFβR1), Alk6 (BMPR1B), and Alk7 (ACVR1C) act as type 1 receptors, whereas BMP receptor 2 (BMPRII), Activin receptor 2 (ActR2), Activin receptor 2A/Activin receptor 2B (ActR2A/2B), and TGFβ receptor 2 (TGFβRII) are the type 2 receptors (Kaivo-oja et al. 2006; Loomans and Andl 2016). Out of seven type 1 receptors, three receptors bind and interact with BMP ligands; BMPR1A, BMPR1B, and ActR1A (Horbelt et al. 2012). Out of five type 2 receptors, three receptors are known to interact with BMP ligands; BMPRII, ActR2A, and ActR2B (Wang et al. 2014). These BMP factors interact with hetero-tetrameric complexes of type 1 and type 2 receptors. Type 2 receptor phosphorylates the type 1 receptor. Once phosphorylated, the type 1 receptor phosphorylates one of the receptor-regulated intracellular signaling SMAD proteins (either SMAD1, -5 and -8). Hence, the phosphorylated BMP receptor-regulated SMADs hetero-dimerizes with common SMAD4 and translocate into the nucleus, where these hetero-complexes act as a transcriptional activator to regulate the expression of the target genes (Massagué 1998, 2000; Souza et al. 2004). Interaction of the BMP, TGFβ, and GDF ligands to their respective receptors have been mentioned in Figure 1A-C.