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Activin A

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https://www.readbyqxmd.com/read/28103859/treatment-with-soluble-activin-type-iib-receptor-improves-bone-mass-and-strength-in-a-mouse-model-of-duchenne-muscular-dystrophy
#1
Tero Puolakkainen, Hongqian Ma, Heikki Kainulainen, Arja Pasternack, Timo Rantalainen, Olli Ritvos, Kristiina Heikinheimo, Juha J Hulmi, Riku Kiviranta
BACKGROUND: Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. METHODS: Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks...
January 19, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28103025/identification-of-the-first-selective-activin-receptor-like-kinase-1-inhibitor-a-reversible-version-of-l-783277
#2
Hanna Cho, Sandip Sengupta, Sean Sh Jeon, Wooyoung Hur, Hwan Geun Choi, Hong Seog Seo, Byung Joo Lee, Jeong Hun Kim, Minhwan Chung, Noo Li Jeon, Nam Doo Kim, Taebo Sim
We synthesized 1 (San78-130), a reversible version of L-783277, as a selective and potent ALK1 inhibitor. Our study showed that 1 possesses great kinase selectivity against a panel of 342 kinases and more potent activity against ALK1 than L-783277. Among the six ALK isotypes (ALK1-6), ALK1 is most significantly inhibited by compound 1. Compound 1 suppresses the BMP9-induced Smad1/5 pathway by mainly inhibiting ALK1 in C2C12 cells. Our molecular dynamics simulations suggest that H-bonding interaction between the C-4' hydroxyl group of 1 and Arg334 of ALK1 substantially contributes to the ALK1 inhibition...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28101909/efficient-transdifferentiation-of-human-dermal-fibroblasts-into-skeletal-muscle
#3
Selwa Mokhtar Boularaoui, Khaled M A Abdel-Raouf, Noaf Salah Ali Alwahab, Megan E Kondash, George A Truskey, Jeremy Choon Meng Teo, Nicolas Christoforou
Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused due to severe injury, congenital defects, or tumor ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells...
January 18, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28097777/activin-a-in-combination-with-erk1-2-mapk-pathway-inhibition-sustains-propagation-of-mouse-embryonic-stem-cells
#4
Yuhei Ashida, May Nakajima-Koyama, Akira Hirota, Takuya Yamamoto, Eisuke Nishida
The Activin/Nodal/TGF-β signaling pathway plays a major role in maintaining mouse epiblast stem cells (EpiSCs). The EpiSC-maintaining medium, which contains Activin A and bFGF, induces differentiation of mouse embryonic stem cells (ESCs) to EpiSCs. Here, we show that Activin A also has an ability to efficiently propagate ESCs without differentiation to EpiSCs when combined with a MEK inhibitor PD0325901. ESCs cultured in Activin+PD retained high-level expression of naive pluripotency-related transcription factors...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28095743/adult-murine-pancreatic-progenitors-require-egf-and-nicotinamide-for-self-renewal-and-differentiation-in-a-serum-and-conditioned-medium-free-culture
#5
Lena Wedeken, Angela Luo, Jacob R Tremblay, Jeffrey Rawson, Liang Jin, Dan Gao, Janine Quijano, Hsun Teresa Ku
Adult pancreatic stem and progenitor cells may serve as an alternative source of insulin-secreting endocrine cells in cell replacement therapy for type 1 diabetes, but much remained unknown about these cells. We previously identified adult murine pancreatic progenitor-like cells that displayed in vitro self-renewal and tri-lineage differentiation activities in a 3-dimensional colony/organoid assay containing 1% methylcellulose and 5% Matrigel. However, the presence of other undefined culture components, such as serum and conditioned medium, has prevented a complete understanding of the signals required for progenitor cell growth...
January 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#6
Maria Gavriatopoulou, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos
Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity. Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28081250/cutaneous-deficiency-of-filaggrin-and-stat3-exacerbates-vaccinia-disease-in-vivo
#7
Yong He, Ishrat Sultana, Kazuyo Takeda, Jennifer L Reed
RATIONALE: Defects in filaggrin and STAT3 are associated with atopic dermatitis (AD) and susceptibility to severe skin infection. METHODS: We evaluated skin infection with the current smallpox vaccine, ACAM-2000, in immunosuppressed mice with combined cutaneous deficiency in filaggrin and STAT3. In parallel, early events post-infection with ACAM-2000 were investigated in cultured keratinocytes in which filaggrin expression was knocked down via siRNA. RESULTS: Immunosuppressed, filaggrin-deficient mice, treated with the topical STAT3 inhibitor Stattic® prior to ACAM-2000 infection, demonstrated rapid weight loss, prolonged vaccinia burden in skin, and dermatitis...
2017: PloS One
https://www.readbyqxmd.com/read/28075462/dnalk2-inhibits-the-proliferation-and-invasiveness-of-breast-cancer-mda-mb-231-cells-through-the-smad-dependent-pathway
#8
Ke Wang, Xiaoxiao Sun, Hong Lei Feng, Chang Fei, Yan Zhang
Breast cancer is one of the most common malignant neoplasms diagnosed in females worldwide. Bone morphogenetic proteins (BMPs), which belong to the TGF-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration and apoptosis in breast cancer. BMPs can bind to type I and II serine/threonine kinase receptors to regulate cell proliferation, invasion, migration, and apoptosis. Type I receptors are expressed in various breast cancer cell lines and primary tumor samples...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28069901/bmp15-regulates-the-inhibin-activin-system-independently-of-ovulation-rate-control-in-sheep
#9
Anthony Estienne, Belén Lahoz, Peggy Jarrier, Loys Bodin, José Folch, José Luis Alabart, Stephane Fabre, Danielle Monniaux
Polymorphisms in the gene encoding bone morphogenetic protein 15 (BMP15) have been associated with multiple ovulations in sheep. As BMP15 regulates inhibin expression in rodents, we assumed that the ovarian inhibin/activin system could mediate part of the effect of BMP15 mutations in the regulation of ovulation rate in sheep. To answer this question, we have studied the effects of two natural loss-of-function mutations of BMP15 on the expression of components of this system. The FecX(R) and the FecX(Gr) mutations, when present respectively in Rasa Aragonesa ewes at the heterozygous state and in Grivette ewes at the homozygous state, were associated with a two-fold increase in ovulation rate...
January 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28065797/characterising-the-developmental-profile-of-hesc-derived-medium-spiny-neuron-progenitors-and-assessing-mature-neuron-function-using-a-crispr-generated-human-darpp-32-wt-egfp-amp-reporter-line
#10
C P J Hunt, C W Pouton, J M Haynes
In the developing ventral telencephalon, cells of the lateral ganglionic eminence (LGE) give rise to all medium spiny neurons (MSNs). This development occurs in response to a highly orchestrated series of morphogenetic stimuli that pattern the resultant neurons as they develop. Striatal MSNs are characterised by expression of dopamine receptors, dopamine-and cyclic AMP-regulated phosphoprotein (DARPP32) and the neurotransmitter GABA. In this study, we demonstrate that fine tuning WNT and SHH signaling early in human embryonic stem cell differentiation can induce a subpallial progenitor molecular profile...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28064277/smad2-phosphorylation-in-diabetic-kidney-tubule-epithelial-cells-is-associated-with-modulation-of-several-transforming-growth-factor-%C3%AE-family-members
#11
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
BACKGROUND: The role of transforming growth factor-β (TGF-β) has recently gained much attention in diabetic nephropathy and kidney fibrosis. In this study, we extend this to an assessment of transcriptional regulation of the entire TGF-β superfamily in kidneys from diabetic vs. healthy mice. In order to study the translation between mouse model and patients, we evaluated the signature of phosphorylated Sma- and Mad-related protein 2 (pSmad2), as molecular marker of TGF-β/activin activity, in the kidneys of streptozotocin (STZ)-treated mice compared to that of type 1 diabetes (T1D) patients...
January 7, 2017: Nephron
https://www.readbyqxmd.com/read/28062564/tgf-%C3%AE-bone-morphogenetic-protein-and-activin-signaling-and-the-tumor-microenvironment
#12
Michael W Pickup, Philip Owens, Harold L Moses
The cellular and noncellular components surrounding the tumor cells influence many aspects of tumor progression. Transforming growth factor β (TGF-β), bone morphogenetic proteins (BMPs), and activins have been shown to regulate the phenotype and functions of the microenvironment and are attractive targets to attenuate protumorigenic microenvironmental changes. Given the pleiotropic nature of the cytokines involved, a full understanding of their effects on numerous cell types in many contexts is necessary for proper clinical intervention...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28050384/inflammatory-myofibroblastic-tumor-of-the-kidney-a-rare-renal-tumor
#13
Alvin Jose Pothadiyil, Suresh Bhat, Fredrick Paul, Jithesh Mampatta, Mahesh Srinivas
Inflammatory Myofibroblastic Tumour (IMT) or 'pseudotumour' of the kidney is a rare benign tumour of unknown aetiology affecting mostly young adults. A subset of IMT is neoplastic and harbours translocations of activin receptor-like kinase-1 (ALK-1) gene and can recur or rarely metastasize. Presentation varies from an incidentaloma to gross haematuria. Clinical examination and radiological investigations are usually inconclusive. Often, biopsy is inconclusive necessitating a management similar to that of Renal Cell Cancer (RCC)...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28049800/activin-a-stock-solution-10-%C3%A2%C2%B5g-ml
#14
(no author information available yet)
No abstract text is available yet for this article.
January 3, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28046097/glucocorticoid-insensitivity-in-virally-infected-airway-epithelial-cells-is-dependent-on-transforming-growth-factor-%C3%AE-activity
#15
Yuxiu C Xia, Asmaa Radwan, Christine R Keenan, Shenna Y Langenbach, Meina Li, Danica Radojicic, Sarah L Londrigan, Rosa C Gualano, Alastair G Stewart
Asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly associated with respiratory syncytial virus (RSV), rhinovirus (RV) and influenza A virus (IAV) infection. The ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (GCs). Viral infection elicits transforming growth factor-β (TGF-β) activity, a growth factor we have previously shown to impair GC action in human airway epithelial cells through the activation of activin-like kinase 5 (ALK5), the type 1 receptor of TGF-β...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28044939/inhibition-of-tgf-%C3%AE-signaling-in-tumor-cells-by-small-molecule-src-family-kinase-inhibitors
#16
Tobias Bartscht, Benjamin Rosien, Dirk Rades, Roland Kaufmann, Harald Biersack, Hendrik Lehnerta, Hendrik Ungefroren
In a series of studies carried out over the last couple of years in various cell types, it was observed that the experimentally used Src family kinase inhibitors PP1 and PP2 and the clinically used Src/Abl inhibitors AZM475271 and dasatinib are potent inhibitors of TGF-β mediated cellular responses such as Smad and p38 mitogen-activated protein kinase phosphorylation, Smad-dependent transcriptional activation, growth inhibition, epithelial-mesenchymal transition (EMT), and cell motility. While for PP1/PP2 it was demonstrated shown that these agents directly inhibit the kinase activity of the TGF-β type I receptor activin receptor-like kinase 5, the mechanism of the anti-TGF-β effect of AZM475271 and dasatinib is less clear...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28035406/bambi-inhibits-inflammation-through-the-activation-of-autophagy-in-experimental-spinal-cord-injury
#17
Yin Yang, Chunyang Guo, Bo Liao, Junjun Cao, Chen Liang, Xijing He
Autophagy plays an important role in the progression of spinal cord injury (SCI). In this study, we aimed to examine the effects and potential mechanisms of action of BMP and activin membrane-bound inhibitor (BAMBI) in the progression of SCI. A rat model of SCI was established and the rats were injected with pLentiH1-BAMBI shRNA and pAd-BAMBI in the gray and white matter of the spinal cord at T8. After 14 days, motor function evaluation was measured according to the Basso Beattie Bresnahan (BBB) method and the number of motor neuron cell accounts in the anterior horns was measured by Nissl staining...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28035346/diet-induced-weight-loss-is-sufficient-to-reduce-senescent-cell-number-in-white-adipose-tissue-of-weight-cycled-mice
#18
Edward O List, Elizabeth Jensen, Jesse Kowalski, Mathew Buchman, Darlene E Berryman, John J Kopchick
Previously, our laboratory reported that weight-cycled mice outlive their obese counterparts. To gain a better mechanistic understanding of these results, we evaluated cellular senescence in white adipose tissue (WAT) of lean, obese, and weight cycled mice. Our results show that at the end of a 28 day weight loss cycle cellular senescence is significantly reduced in multiple WAT depots compared to obese mice, which also corresponds to a reduction in circulating activin A (a marker of senescence). These findings suggest that a previously undescribed benefit to weight loss may be a reduction of cellular senescence in WAT...
October 27, 2016: Nutr Healthy Aging
https://www.readbyqxmd.com/read/28032440/magnolol-attenuates-concanavalin-a-induced-hepatic-fibrosis-inhibits-cd4-t-helper-17-th17-cell-differentiation-and-suppresses-hepatic-stellate-cell-activation-blockade-of-smad3-smad4-signalling
#19
Hongjun Zhang, Baoling Ju, Xiaoli Zhang, Yanfei Zhu, Ying Nie, Yuanhong Xu, Qiuxia Lei
Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo...
December 29, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28031424/the-dart-study-results-from-the-dose-escalation-and-expansion-cohorts-evaluating-the-combination-of-dalantercept-plus-axitinib-in-advanced-renal-cell-carcinoma
#20
Martin H Voss, Rupal S Bhatt, Elizabeth R Plimack, Brian I Rini, Robert S Alter, J Thaddeus Beck, Dawn Wilson, Xiaosha Zhang, Musa Mutyaba, Chad Glasser, Kenneth M Attie, Matthew L Sherman, Shuchi S Pandya, Michael Atkins
PURPOSE: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis. Concurrent targeting of ALK1 and vascular endothelial growth factor (VEGF) signaling results in augmented inhibition of tumor growth in renal cell carcinoma (RCC) xenograft models. Dalantercept is an ALK1 receptor-fusion protein that acts as a ligand trap for bone morphogenetic proteins (BMP) 9 and 10. The DART Study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept plus axitinib in patients with advanced RCC and determined the optimal dose for further testing...
December 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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