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https://www.readbyqxmd.com/read/29140406/smad3-stat3-crosstalk-in-pathophysiological-contexts
#1
Yuka Itoh, Masao Saitoh, Keiji Miyazawa
Smad3 and STAT3 are intracellular molecules that transmit signals from plasma membrane receptors to the nucleus. Smad3 operates downstream of growth/differentiation factors that utilize activin receptor-like kinase (ALK)-4, 5, or 7, such as transforming growth factor-β (TGF-β), activin, and myostatin. STAT3 principally functions downstream of cytokines that exert their effects via gp130 and Janus family kinases, including interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M. Accumulating evidence indicates that Smad3 and STAT3 engage in crosstalk in a highly context-dependent fashion, cooperating in some conditions while acting antagonistically each other in others...
November 13, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29140249/maternal-gdf3-is-an-obligatory-cofactor-in-nodal-signaling-for-embryonic-axis-formation-in-zebrafish
#2
Brent W Bisgrove, Yi-Chu Su, H Joseph Yost
Zebrafish Gdf3 (Dvr1) is a member of the TGFb superfamily of cell signaling ligands that includes Xenopus Vg1 and mammalian Gdf1/3. Surprisingly, engineered homozygous mutants in zebrafish have no apparent phenotype. Elimination of Gdf3 in oocytes of maternal-zygotic mutants results in embryonic lethality that can be fully rescued with gdf3 RNA, demonstrating that Gdf3 is required only early in development, beyond which mutants are viable and fertile. Gdf3 mutants are refractory to Nodal ligands and Nodal repressor Lefty1...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29113826/ghrelin-suppresses-cardiac-fibrosis-of-post-myocardial-infarction-heart-failure-rats-by-adjusting-the-activin-a-follistatin-imbalance
#3
Chunyan Yang, Jinsha Liu, Kai Liu, Beibei Du, Kaiyao Shi, Mei Ding, Bing Li, Ping Yang
Ghrelin, a growth hormone-releasing peptide, potentially improves cardiac function, but the mechanisms remain unclear. In the study, the rat heart failure (HF) model was established by ligating the left anterior descending coronary artery (LAD) and treated with ghrelin (100μg/kg, subcutaneous injection, bid); neonatal rat cardiomyocytes were cultured and stimulated with Ang II (0.1μM) and ghrelin(0.1μM) to explore the underlying mechanism of ghrelin in myocardial remodeling. Hemodynamic changes and serum brain natriuretic peptide (BNP) concentrations were measured to assess cardiac function...
November 4, 2017: Peptides
https://www.readbyqxmd.com/read/29111388/activin-over-expression-in-the-testis-of-mice-lacking-the-inhibin-%C3%AE-subunit-gene-is-associated-with-androgen-deficiency-and-regression-of-the-male-reproductive-tract
#4
Rukmali Wijayarathna, David M de Kretser, Andreas Meinhardt, Ralf Middendorff, Helen Ludlow, Nigel P Groome, Kate A Loveland, Mark P Hedger
Regionalised interaction of the activins, follistatin and inhibin was investigated in the male reproductive tract of mice lacking the inhibin α-subunit (Inha(-/-)). Serum and intratesticular activin B, although not activin A and follistatin, were increased in Inha(-/-) mice at 25 days of age, but all three proteins were elevated at 56 days. None of these proteins were altered within the epididymis and vas deferens at either age. At 25 days, histology of the epididymis and vas deferens was similar to wild-type...
October 27, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29109273/blockade-of-activin-type-ii-receptors-with-a-dual-anti-actriia-iib-antibody-is-critical-to-promote-maximal-skeletal-muscle-hypertrophy
#5
Frederic Morvan, Jean-Michel Rondeau, Chao Zou, Giulia Minetti, Clemens Scheufler, Meike Scharenberg, Carsten Jacobi, Pascale Brebbia, Veronique Ritter, Gauthier Toussaint, Claudia Koelbing, Xavier Leber, Alain Schilb, Florian Witte, Sylvie Lehmann, Elke Koch, Sabine Geisse, David J Glass, Estelle Lach-Trifilieff
The TGF-β family ligands myostatin, GDF11, and activins are negative regulators of skeletal muscle mass, which have been reported to primarily signal via the ActRIIB receptor on skeletal muscle and thereby induce muscle wasting described as cachexia. Use of a soluble ActRIIB-Fc "trap," to block myostatin pathway signaling in normal or cachectic mice leads to hypertrophy or prevention of muscle loss, perhaps suggesting that the ActRIIB receptor is primarily responsible for muscle growth regulation. Genetic evidence demonstrates however that both ActRIIB- and ActRIIA-deficient mice display a hypertrophic phenotype...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29103804/fibrinogen-activates-bmp-signaling-in-oligodendrocyte-progenitor-cells-and-inhibits-remyelination-after-vascular-damage
#6
Mark A Petersen, Jae Kyu Ryu, Kae-Jiun Chang, Ainhoa Etxeberria, Sophia Bardehle, Andrew S Mendiola, Wanjiru Kamau-Devers, Stephen P J Fancy, Andrea Thor, Eric A Bushong, Bernat Baeza-Raja, Catriona A Syme, Michael D Wu, Pamela E Rios Coronado, Anke Meyer-Franke, Stephanie Yahn, Lauriane Pous, Jae K Lee, Christian Schachtrup, Hans Lassmann, Eric J Huang, May H Han, Martina Absinta, Daniel S Reich, Mark H Ellisman, David H Rowitch, Jonah R Chan, Katerina Akassoglou
Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fate in vitro...
October 19, 2017: Neuron
https://www.readbyqxmd.com/read/29102564/gonadotropin-regulation-by-pulsatile-gnrh-signaling-and-gene-expression
#7
REVIEW
George A Stamatiades, Ursula B Kaiser
The precise orchestration of hormonal regulation at all levels of the hypothalamic-pituitary-gonadal axis is essential for normal reproductive function and fertility. The pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) stimulates the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by pituitary gonadotropes. GnRH acts by binding to its high affinity seven-transmembrane receptor (GnRHR) on the cell surface of anterior pituitary gonadotropes. Different signaling cascades and transcriptional mechanisms are activated, depending on the variation in GnRH pulse frequency, to stimulate the synthesis and release of FSH and LH...
November 2, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29100238/activin-a-in-inflammation-tissue-repair-and-fibrosis-possible-role-as-inflammatory-and-fibrotic-mediator-of-uterine-fibroid-development-and-growth
#8
Olga Protic, Md Soriful Islam, Stefania Greco, Stefano Raffaele Giannubilo, Pasquale Lamanna, Felice Petraglia, Andrea Ciavattini, Mario Castellucci, Boris Hinz, Pasquapina Ciarmela
No abstract text is available yet for this article.
November 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/29097342/variable-signaling-activity-by-fop-acvr1-mutations
#9
REVIEW
Julia Haupt, Meiqi Xu, Eileen M Shore
Most patients with fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder of heterotopic ossification, have the same causative mutation in ACVR1, R206H. However, additional mutations within the ACVR1 BMP type I receptor have been identified in a small number of FOP cases, often in patients with disease of lesser or greater severity than occurs with R206H mutations. Genotype-phenotype correlations have been suggested in patients, resulting in classification of FOP mutations based on location within different receptor domains and structural modeling...
October 30, 2017: Bone
https://www.readbyqxmd.com/read/29089584/acvr2b-fc-counteracts-chemotherapy-induced-loss-of-muscle-and-bone-mass
#10
Rafael Barreto, Yukiko Kitase, Tsutomu Matsumoto, Fabrizio Pin, Kyra C Colston, Katherine E Couch, Thomas M O'Connell, Marion E Couch, Lynda F Bonewald, Andrea Bonetto
Chemotherapy promotes the development of cachexia, a debilitating condition characterized by muscle and fat loss. ACVR2B/Fc, an inhibitor of the Activin Receptor 2B signaling, has been shown to preserve muscle mass and prolong survival in tumor hosts, and to increase bone mass in models of osteogenesis imperfecta and muscular dystrophy. We compared the effects of ACVR2B/Fc on muscle and bone mass in mice exposed to Folfiri. In addition to impairing muscle mass and function, Folfiri had severe negative effects on bone, as shown by reduced trabecular bone volume fraction (BV/TV), thickness (Tb...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29084242/transforming-growth-factor-%C3%AE-activin-signaling-in-neurons-increases-susceptibility-to-starvation
#11
Wen-Bin Alfred Chng, Rafael Koch, Xiaoxue Li, Shu Kondo, Emi Nagoshi, Bruno Lemaitre
Animals rely on complex signaling network to mobilize its energy stores during starvation. We have previously shown that the sugar-responsive TGFβ/Activin pathway, activated through the TGFβ ligand Dawdle, plays a central role in shaping the post-prandial digestive competence in the Drosophila midgut. Nevertheless, little is known about the TGFβ/Activin signaling in sugar metabolism beyond the midgut. Here, we address the importance of Dawdle (Daw) after carbohydrate ingestion. We found that Daw expression is coupled to dietary glucose through the evolutionarily conserved Mio-Mlx transcriptional complex...
2017: PloS One
https://www.readbyqxmd.com/read/29079832/myostatin-inhibition-prevents-skeletal-muscle-pathophysiology-in-huntington-s-disease-mice
#12
Marie K Bondulich, Nelly Jolinon, Georgina F Osborne, Edward J Smith, Ivan Rattray, Andreas Neueder, Kirupa Sathasivam, Mhoriam Ahmed, Nadira Ali, Agnesska C Benjamin, Xiaoli Chang, James R T Dick, Matthew Ellis, Sophie A Franklin, Daniel Goodwin, Linda Inuabasi, Hayley Lazell, Adam Lehar, Angela Richard-Londt, Jim Rosinski, Donna L Smith, Tobias Wood, Sarah J Tabrizi, Sebastian Brandner, Linda Greensmith, David Howland, Ignacio Munoz-Sanjuan, Se-Jin Lee, Gillian P Bates
Huntington's disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD. Weekly administration from 5 to 11 weeks of age prevented body weight loss, skeletal muscle atrophy, muscle weakness, contractile abnormalities, the loss of functional motor units in EDL muscles and delayed end-stage disease...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29076502/derivation-of-hypermethylated-pluripotent-embryonic-stem-cells-with-high-potency
#13
Siqin Bao, Walfred Wc Tang, Baojiang Wu, Shinseog Kim, Jingyun Li, Lin Li, Toshihiro Kobayashi, Caroline Lee, Yanglin Chen, Mengyi Wei, Shudong Li, Sabine Dietmann, Fuchou Tang, Xihe Li, M Azim Surani
Naive hypomethylated embryonic pluripotent stem cells (ESCs) are developmentally closest to the preimplantation epiblast of blastocysts, with the potential to contribute to all embryonic tissues and the germline, excepting the extra-embryonic tissues in chimeric embryos. By contrast, epiblast stem cells (EpiSCs) resembling postimplantation epiblast are relatively more methylated and show a limited potential for chimerism. Here, for the first time, we reveal advanced pluripotent stem cells (ASCs), which are developmentally beyond the pluripotent cells in the inner cell mass but with higher potency than EpiSCs...
October 27, 2017: Cell Research
https://www.readbyqxmd.com/read/29050936/t%C3%AE-riii-is-induced-by-tcr-signaling-and-downregulated-in-foxp3-regulatory-t-cells
#14
Sandra Ortega-Francisco, Marisol de la Fuente-Granada, Evelyn K Alvarez Salazar, Lizbeth Airais Bolaños-Castro, Gabriela Fonseca-Camarillo, Roxana Olguin-Alor, Germán R Alemán-Muench, Fernando López-Casillas, Chander Raman, Eduardo A García-Zepeda, Gloria Soldevila
TGF-β type III receptor (TβRIII) is a co-receptor for TGFβ family members required for high-affinity binding of these ligands to their receptors, potentiating their cellular functions. TGF-βs, Bone Morphogenetic Proteins (BMP2/4) and Inhibins/Activins regulate different checkpoints during T cell differentiation. We have previously reported that TβRIII modulates T cell development by protecting developing thymocytes from apoptosis, however the role of this co-receptor in peripheral lymphocytes still remains elusive...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29047024/generation-of-photoreceptor-precursors-from-mouse-embryonic-stem-cells
#15
Amy Q Lu, Colin J Barnstable
Embryonic stem cell (ESC) differentiation can be used to model development and to produce transplantable cells of the desired phenotype. ESCs can reproducibly generate retinal cells but the derivation of photoreceptor precursors is variable and depends on an array of exogenous factors and intrinsic cell-cell interactions. In this work, we have defined the use of exogenous signaling factors, dissociation, and adherent versus 3-dimensional (3D) conditions on the derivation of retinal cells from pluripotent mouse ESCs...
October 18, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29044512/differences-in-definitive-endoderm-induction-approaches-using-growth-factors-and-small-molecules
#16
Mariia S Bogacheva, Sofia Khan, Liisa K Kanninen, Marjo Yliperttula, Alan W Leung, Yan-Ru Lou
Definitive endoderm (DE) is the first stage of human pluripotent stem cell (hPSC) differentiation into hepatocyte-like cells. Developing human liver cell models for pharmaceutical applications is highly demanding. Due to the vast number of existing protocols to generate DE cells from hPSCs, we aimed to compare the specificity and efficiency of selected published differentiation conditions. We differentiated two hPSC lines (induced PSC and embryonic stem cell) to DE cells on Matrigel matrix using growth factors (Activin A and Wnt-3a) and small molecules (sodium butyrate and IDE 1) in different combinations...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29030492/comparative-analysis-of-activins-a-and-b-in-the-adult-mouse-epididymis-and-vas-deferens
#17
Rukmali Wijayarathna, David de Kretser, Rajini Sreenivasan, Helen Ludlow, Ralf Middendorff, Andreas Meinhardt, Kate L Loveland, Mark P Hedger
Activin A regulates testicular and epididymal development, but the role of activin B in the epididymis and vas deferens is unknown. Mouse models with reduced activin A (Inhba(+/-) and Inhba(BK/+)), or its complete absence (Inhba(BK/BK)), were investigated to identify specific roles of activins in the male reproductive tract. In 8 week old Inhba(+/-) mice, serum activin A decreased by 70%, with a 50% reduction of gene expression and protein in the testis, epididymis and vas deferens. Activin B and the activin-binding protein, follistatin, were similar to wild-type...
October 13, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29027123/pluripotent-stem-cells-secrete-activin-a-to-improve-their%C3%A2-epiblast-competency-after-injection-into-recipient-embryos
#18
Jinzhu Xiang, Suying Cao, Liang Zhong, Hanning Wang, Yangli Pei, Qingqing Wei, Bingqiang Wen, Haiyuan Mu, Shaopeng Zhang, Liang Yue, Genhua Yue, Bing Lim, Jianyong Han
It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a "dose effect". Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs...
October 12, 2017: Protein & Cell
https://www.readbyqxmd.com/read/29020616/the-emerging-role-of-follistatin-under-stresses-and-its-implications-in-diseases
#19
REVIEW
Lingda Zhang, Kangli Liu, Bing Han, Zhengping Xu, Xiangwei Gao
Follistatin (FST), a single-chain glycosylated protein, is expressed in various tissues. The essential biological function of FST is binding and neutralizing transforming growth factor β (TGF-β) superfamily, including activin, myostatin, and bone morphogenetic protein (BMP). Emerging evidence indicates that FST also serves as a stress responsive protein, which plays a protective role under a variety of stresses. In most cases, FST performs the protective function through its neutralization of TGF-β superfamily...
October 8, 2017: Gene
https://www.readbyqxmd.com/read/28989145/-clinical-and-genetic-diagnosis-in-a-hereditary-hemorrhagic-telangiectasia-family
#20
Yan Yi, Xiaofeng Liu, Boda Wu, Jun Liu, Shenglei Ge, Xiaoliu Shi
To investigate the clinical features and feasibility genetic diagnosis in a hereditary hemorrhagic telangiectasia (HHT) family, and to explore the application of gene mutation testing in HHT diagnosis.
 Methods: Medical histories and clinical features of a family were analyzed to diagnose HHT patients and suspected individuals according to the clinical diagnostic criteria. Sequence analysis of endoglin (ENG) and activin A receptor like type 1 (ACVRL1) gene in the proband was performed with PCR and Sanger sequencing technology...
September 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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