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Activin A

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https://www.readbyqxmd.com/read/29789425/a-heterodimer-formed-by-bone-morphogenetic-protein-9-bmp9-and-bmp10-provides-most-bmp-biological-activity-in-plasma
#1
Emmanuelle Tillet, Marie Ouarné, Agnès Desroches-Castan, Christine Mallet, Mariela Subileau, Robin Didier, Anna Lioutsko, Guillaume Belthier, Jean-Jacques Feige, Sabine Bailly
Bone morphogenetic protein 9 (BMP9) and BMP10 are the two high-affinity ligands for the endothelial receptor activin receptor-like kinase 1 (ALK1) and are key regulators of vascular remodeling. They are both present in the blood, but their respective biological activities are still a matter of debate. The aim of the present work was to characterize their circulating forms to better understand how their activities are regulated in vivo. First, by cotransfecting BMP9 and BMP10, we found that both can form a disulfide-bonded heterodimer in vitro and that this heterodimer is functional on endothelial cells via ALK1...
May 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29766570/melatonin-improves-endothelial-function-in-vitro-and-prolongs-pregnancy-in-women-with-early-onset-preeclampsia
#2
Sebastian R Hobson, Seshi Gurusinghe, Rebecca Lim, Nicole O Alers, Suzanne L Miller, John C Kingdom, Euan M Wallace
Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine if melatonin could be a useful adjuvant therapy. In a xanthine/xanthine oxidase (X/XO) placental explant model, melatonin reduced oxidative stress (8-isoprostane) and enhanced antioxidant markers (Nrf2 translocation, HO-1), but did not affect explant production of anti-angiogenic factors (sFlt, sEng, activin A)...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29752954/regulation-of-the-activins-follistatins-inhibins-axis-by-energy-status-impact-on-reproductive-function
#3
Nikolaos Perakakis, Jagriti Upadhyay, Wael Ghaly, Joyce Chen, Pavlina Chrysafi, Athanasios D Anastasilakis, Christos S Mantzoros
BACKGROUND: We have previously demonstrated that the adipose tissue derived hormone leptin controls reproductive function by regulating the hypothalamic-pituitary-gonadal axis in response to energy deficiency. Here, we evaluate the activins-follistatins-inhibins (AFI) axis during acute (short-term fasting in healthy people) and chronic energy deficiency (women with hypothalamic amenorrhea due to strenuous exercise [HA]) and investigate their relation to leptin and reproductive function in healthy subjects and subjects with HA...
May 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29752426/protein-engineering-on-human-recombinant-follistatin-enhancing-pharmacokinetic-characteristics-for-therapeutic-application
#4
Chuan Shen, Andrea Iskenderian, Dianna Lundberg, Tao He, Kathleen Palmieri, Robert Crooker, Qingwei Deng, Matthew Traylor, Sheng Gu, Haojing Rong, David Ehmann, Brian Pescatore, Bettina Strack-Logue, Alla Romashko, George Baviello, John Gill, Bohong Zhang, Muthuraman Meiyappan, Clark Pan, Angela W Norton
Follistatin (FS) is an important regulatory protein, a natural antagonist for transforming growth factor beta family members activin and myostatin. The diverse biological roles of the activin and myostatin signaling pathways make FS a promising therapeutic target for treating human diseases exhibiting inflammation, fibrosis and muscle disorders, such as Duchenne muscular dystrophy. However, rapid heparin-mediated hepatic clearance of FS limits its therapeutic potential. We targeted the heparin binding loop of FS for site-directed mutagenesis to improve clearance parameters...
May 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29751359/bone-morphogenetic-protein-9-as-a-key-regulator-of-liver-progenitor-cells-in-ddc-induced-cholestatic-liver-injury
#5
Annalisa Addante, Cesáreo Roncero, Laura Almalé, Nerea Lazcanoiturburu, María García-Álvaro, Margarita Fernández, Julián Sanz, Seddik Hammad, Zeribe Chike Nwosu, Se-Jin Lee, Isabel Fabregat, Steven Dooley, Peter Ten Dijke, Blanca Herrera, Aránzazu Sánchez
BACKGROUND & AIMS: Bone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion. METHODS: WT and BMP9KO mice were submitted to DDC diet...
May 11, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29743313/ivig-promote-cross-tolerance-against-inflammatory-stimuli-in-vitro-and-in-vivo
#6
Ángeles Domínguez-Soto, Miriam Simón-Fuentes, Mateo de Las Casas-Engel, Víctor D Cuevas, María López-Bravo, Jorge Domínguez-Andrés, Paula Saz-Leal, David Sancho, Carlos Ardavín, Juliana Ochoa-Grullón, Silvia Sánchez-Ramón, Miguel A Vega, Angel L Corbí
IVIg is an approved therapy for immunodeficiency and for several autoimmune and inflammatory diseases. However, the molecular basis for the IVIg anti-inflammatory activity remains to be fully explained and cannot be extrapolated from studies on animal models of disease. We now report that IVIg impairs the generation of human monocyte-derived anti-inflammatory macrophages by inducing JNK activation and activin A production and limits proinflammatory macrophage differentiation by inhibiting GM-CSF-driven STAT5 activation...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29739878/bmpr2-inhibits-activin-and-bmp-signaling-via-wild-type-alk2
#7
Oddrun Elise Olsen, Meenu Sankar, Samah Elsaadi, Hanne Hella, Glenn Buene, Sagar Ramesh Darvekar, Kristine Misund, Takenobu Katagiri, Petra Knaus, Toril Holien
TGF-β/BMP superfamily ligands require heteromeric complexes of type 1 and 2 receptors for ligand dependent downstream signaling. Activin A, a TGF-β superfamily member, inhibits growth of multiple myeloma cells, but the mechanism is unknown. We aimed to clarify how activins affect myeloma cell survival. Activin A activates the transcription factors SMAD2/3 through the ALK4 type 1 receptor, but may also activate SMAD1/5/8 through mutated variants of the type 1 receptor ALK2. We demonstrate that activin A and B activate SMAD1/5/8 in myeloma cells through endogenous wild type ALK2...
May 8, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29737562/mechanisms-involved-in-enhancement-of-osteoclast-formation-by-activin-a
#8
Tomonari Kajita, Wataru Ariyoshi, Toshinori Okinaga, Sho Mitsugi, Kazuhiro Tominaga, Tatsuji Nishihara
Several growth factors in bone tissues are reported to be associated with osteoclastogenesis. Activin-A, a member of the transforming growth factor-β (TGF-β) family is known to be present in bone tissues and an important regulator in osteoclastogenesis with SMAD-mediated signaling being crucial for inducing osteoclast differentiation. In the present study, we examined the effect and underlying mechanisms of activin-A on osteoclast formation in vitro culture systems. Activin-A enhanced osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW 264...
May 8, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29733462/current-and-potential-therapeutic-strategies-for-the-management-of-vascular-calcification-in-patients-with-chronic-kidney-disease-including-those-on-dialysis
#9
REVIEW
Irene Ruderman, Stephen G Holt, Tim D Hewitson, Edward R Smith, Nigel D Toussaint
Patients with CKD have accelerated vascular stiffening contributing significantly to excess cardiovascular morbidity and mortality. Much of the arterial stiffening is thought to involve vascular calcification (VC), but the pathogenesis of this phenomenon is complex, resulting from a disruption of the balance between promoters and inhibitors of calcification in a uremic milieu, along with derangements in calcium and phosphate metabolic pathways. Management of traditional cardiovascular risk factors to reduce VC may be influential but has not been shown to significantly improve mortality...
May 7, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29731967/anti-cachectic-effect-of-antrodia-cinnamomea-extract-in-lung-tumor-bearing-mice-under-chemotherapy
#10
Meng-Chuan Chen, Wen-Lin Hsu, Tz-Chong Chou
Skeletal muscle atrophy, the most characteristic feature of cancer cachexia, often occurs in patients with cancer undergoing chemotherapy. Antrodia cinnamomea (AC) a widely used edible medical fungus, exhibits hepatoprotective, anti-inflammatory and anticancer activities. In this study, we investigated whether combined treatment with the ethonolic extract of AC ameliorates cachexia symptoms, especially muscle wasting, in lung tumor-bearing mice treated with chemotherapy. Our results revealed that gemcitabine and cisplatin-induced severe body weight loss and skeletal muscle atrophy in the mice with cancer were greatly attenuated after AC extract administration...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29726548/commentary-blockade-of-activin-type-ii-receptors-with-a-dual-anti-actriia-iib-antibody-is-critical-to-promote-maximal-skeletal-muscle-hypertrophy
#11
COMMENT
Javier Durán, Manuel Estrada
No abstract text is available yet for this article.
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29722201/treating-cachexia-using-soluble-acvr2b-improves-survival-alters-mtor-localization-and-attenuates-liver-and-spleen-responses
#12
Tuuli A Nissinen, Jaakko Hentilä, Fabio Penna, Anita Lampinen, Juulia H Lautaoja, Vasco Fachada, Tanja Holopainen, Olli Ritvos, Riikka Kivelä, Juha J Hulmi
BACKGROUND: Cancer cachexia increases morbidity and mortality, and blocking of activin receptor ligands has improved survival in experimental cancer. However, the underlying mechanisms have not yet been fully uncovered. METHODS: The effects of blocking activin receptor type 2 (ACVR2) ligands on both muscle and non-muscle tissues were investigated in a preclinical model of cancer cachexia using a recombinant soluble ACVR2B (sACVR2B-Fc). Treatment with sACVR2B-Fc was applied either only before the tumour formation or with continued treatment both before and after tumour formation...
May 2, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29716627/microrna-424-503-cluster-members-regulate-bovine-granulosa-cell-proliferation-and-cell-cycle-progression-by-targeting-smad7-gene-through-activin-signalling-pathway
#13
Hari Om Pande, Dawit Tesfaye, Michael Hoelker, Samuel Gebremedhn, Eva Held, Christiane Neuhoff, Ernst Tholen, Karl Schellander, Dessie Salilew Wondim
BACKGROUND: The granulosa cells are indispensable for follicular development and its function is orchestrated by several genes, which in turn posttranscriptionally regulated by microRNAs (miRNA). In our previous study, the miRRNA-424/503 cluster was found to be highly abundant in bovine granulosa cells (bGCs) of preovulatory dominant follicle compared to subordinate counterpart at day 19 of the bovine estrous cycle. Other study also indicated the involvement of miR-424/503 cluster in tumour cell resistance to apoptosis suggesting this miRNA cluster may involve in cell survival...
May 1, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29699384/tgf-%C3%AE-induces-smad2-phosphorylation-are-induction-and-trophoblast-differentiation
#14
Renee E Albers, Kaisa Selesniemi, David R C Natale, Thomas L Brown
Background: Transforming growth factor beta (TGF-β) signaling has been shown to control a large number of critical cellular actions such as cell death, differentiation, and development and has been implicated as a major regulator of placental function. SM10 cells are a mouse placental progenitor cell line, which has been previously shown to differentiate into nutrient transporting, labyrinthine-like cells upon treatment with TGF-β. However, the signal transduction pathway activated by TGF-β to induce SM10 progenitor differentiation has yet to be fully investigated...
April 30, 2018: International Journal of Stem Cells
https://www.readbyqxmd.com/read/29693185/microrna-384-inhibits-the-progression-of-breast-cancer-by-targeting-acvr1
#15
Yongxia Wang, Zheying Zhang, Jianqiang Wang
Breast cancer is the leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancer cases and has a poorer prognosis than other subtypes. Moreover, the treatment for breast cancer, especially for TNBC, remains unsatisfactory. Therefore, novel therapies are urgently needed. Microribonucleic acids (miRNAs) are a class of biomarkers and therapeutic targets in many types of cancers. In the present study, the expression of miR-384 was explored in GSE58606 and in fresh breast cancer tissues by qPCR...
April 20, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29685894/bambi-is-a-novel-hif1-dependent-modulator-of-tgf%C3%AE-mediated-disruption-of-cell-polarity-in-hypoxia
#16
Irina Raykhel, Fazeh Moafi, Satu M Myllymäki, Patricia G Greciano, Karl S Matlin, Jose V Moyano, Aki Manninen, Johanna Myllyharju
Hypoxia and loss of cell polarity are common features of malignant carcinomas. Hypoxia-inducible factor 1 (HIF1) is the major regulator of cellular hypoxia response through activation of ∼300 genes. Increased HIF1 signaling is known to be associated with epithelial-mesenchymal transformation. Here we report that hypoxia disrupts polarized epithelial morphogenesis of MDCK cells in HIF1α-dependent manner by modulating the transforming growth factor β (TGFβ) signaling pathway. Analysis of potential HIF1 targets in the TGFβ pathway identified the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a transmembrane glycoprotein related to the type I receptors of the TGFβ family, whose expression was essentially lost in HIF1-depleted cells...
April 23, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29682722/the-role-of-tgf-%C3%AE-in-th17-differentiation
#17
REVIEW
Song Zhang
Th17 cells play critical roles in inflammatory and autoimmune diseases. The lineage-specific transcription factor RORγt is the key regulator for Th17 cell fate commitment. A substantial number of studies have established the importance of TGF-β-dependent pathways in inducing RORγt expression and Th17 differentiation. TGF-β superfamily members TGF-β1, TGF-β3, or activin A, in concert with IL-6 or IL-21 differentiate naïve T cells into Th17 cells. Alternatively, Th17 differentiation can occur through TGF-β-independent pathways...
April 23, 2018: Immunology
https://www.readbyqxmd.com/read/29671950/comparative-transcriptomics-across-14-drosophila-species-reveals-signatures-of-longevity
#18
Siming Ma, Andrei S Avanesov, Emily Porter, Byung Cheon Lee, Marco Mariotti, Nadezhda Zemskaya, Roderic Guigo, Alexey A Moskalev, Vadim N Gladyshev
Lifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life-history traits and transcriptomes of 14 Drosophila species differing more than sixfold in lifespan, we explored expression divergence and identified genes and processes that correlate with longevity. These longevity signatures suggested that longer-lived flies upregulate fatty acid metabolism, downregulate neuronal system development and activin signaling, and alter dynamics of RNA splicing...
April 19, 2018: Aging Cell
https://www.readbyqxmd.com/read/29671342/human-articular-chondrocytes-retain-their-phenotype-in-sustained-hypoxia-while-normoxia-promotes-their-immunomodulatory-potential
#19
Claire Mennan, John Garcia, Helen McCarthy, Sharon Owen, Jade Perry, Karina Wright, Robin Banerjee, James B Richardson, Sally Roberts
Objective To assess the phenotype of human articular chondrocytes cultured in normoxia (21% O2 ) or continuous hypoxia (2% O2 ). Design Chondrocytes were extracted from patients undergoing total knee replacement ( n = 5) and cultured in ~21% (normoxic chondrocytes, NC) and 2% (hypoxic chondrocytes, HC) oxygen in both monolayer and 3-dimensional (3D) pellet culture and compared with freshly isolated chondrocytes (FC). Cells were assessed by flow cytometry for markers indicative of mesenchymal stromal cells (MSCs), chondrogenic-potency and dedifferentiation...
April 1, 2018: Cartilage
https://www.readbyqxmd.com/read/29656291/activin-a-is-a-pro-inflammatory-regulator-in-type-2-driven-upper-airway-disease
#20
Adam M Chaker, Ulrich Matthias Zissler, Nikolaos Poulos, Martin Wagenmann, Murat Bas, Ferdinand Gürth, Georgina Xanthou, Carsten Schmidt-Weber
BACKGROUND: Allergic upper airway disease involves pro-inflammatory type-2 cytokines such as IL-5 and regulatory tissue repair mediators, in particular transforming growth factor (TGF)-β1. The TGF-β-superfamily member activin-A displays multiple biological functions and shares certain signalling pathways with TGF-β1. We aimed to examine the coregulation of mucosal activin-A and TGF-β1 in acute allergic and chronic Th2-driven upper airway disease. METHODS: We investigated mucosal cytokine expression profiles and kinetics using RT-PCR after nasal allergen challenges in patients with seasonal allergic rhinitis...
April 13, 2018: International Archives of Allergy and Immunology
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