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Activin A

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https://www.readbyqxmd.com/read/28647906/exogenous-gdf11-induces-cardiac-and-skeletal-muscle-dysfunction-and-wasting
#1
Teresa A Zimmers, Yanling Jiang, Meijing Wang, Tiffany W Liang, Joseph E Rupert, Ernie D Au, Francesco E Marino, Marion E Couch, Leonidas G Koniaris
Growth differentiation factor 11 (GDF11), a TGF-beta superfamily member, is highly homologous to myostatin and essential for embryonic patterning and organogenesis. Reports of GDF11 effects on adult tissues are conflicting, with some describing anti-aging and pro-regenerative activities on the heart and skeletal muscle while others opposite or no effects. Herein, we sought to determine the in vivo cardiac and skeletal muscle effects of excess GDF11. Mice were injected with GDF11 secreting cells, an identical model to that used to initially identify the in vivo effects of myostatin...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28647698/increased-expression-of-follistatin-in-breast-cancer-reduces-invasiveness-and-clinically-correlates-with-better-survival
#2
Catherine Zabkiewicz, Jeyna Resaul, Rachel Hargest, Wen Guo Jiang, Lin Ye
BACKGROUND/AIM: Activin and its antagonist follistatin (FST) have been implicated in several solid tumours. This study investigated the role of FST in breast cancer. MATERIALS AND METHODS: FST expression was examined using reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry in a cohort of breast cancer samples. Expression was correlated to pathological and prognostic parameters in our patient cohort...
July 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28646109/bone-morphogenetic-protein-bmp-9-and-bmp10-enhance-tumor-necrosis-factor-%C3%AE-induced-monocyte-recruitment-to-the-vascular-endothelium-mainly-via-activin-receptor-like-kinase-2
#3
Claudia-Gabriela Mitrofan, Sarah L Appleby, Gerard B Nash, Ziad Mallat, Edwin R Chilvers, Paul D Upton, Nicholas W Morrell
Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an in vitro flow adhesion assay. Herein, we report that while BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergised with Tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with upregulated expression levels of E-selectin, VCAM-1 and ICAM-1 on endothelial cells...
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28643356/bimagrumab-improves-body-composition-and-insulin-sensitivity-in-insulin-resistant-subjects
#4
Tania Garito, Ronenn Roubenoff, Marcus Hompesch, Linda Morrow, Katherine Gomez, Daniel Rooks, Charles Meyers, Monte Buchsbaum, Srikanth Neelakantham, Therese Swan, Lee Anne Filosa, Didier Laurent, Olivier Petricoul, Marjorie Zakaria
BACKGROUND: Skeletal muscle is a key mediator of insulin resistance. Bimagrumab, an antibody against activin receptor type II (ActRII), prevents binding of negative muscle regulators, like myostatin, and increases lean mass and decreases fat mass in animal models. OBJECTIVE: We hypothesized that an improving body composition in insulin resistant individuals could enhance insulin sensitivity. METHODS: Sixteen individuals with mean body mass index (BMI) = 29...
June 23, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28639003/the-crucial-role-of-activin-a-alk4-pathway-in-the-pathogenesis-of-ang-ii-induced-atrial-fibrosis-and-vulnerability-to-atrial-fibrillation
#5
Qian Wang, Ying Yu, Pengpai Zhang, Yihe Chen, Changyi Li, Jie Chen, Yuepeng Wang, Yigang Li
Atrial fibrosis, the hallmark of structural remodeling associated with atrial fibrillation (AF), is characterized by abnormal proliferation of atrial fibroblasts and excessive deposition of extracellular matrix. Transforming growth factor-β1 (TGF-β1)/activin receptor-like kinase 5 (ALK5)/Smad2/3/4 pathway has been reported to be involved in the process. Recent studies have implicated both activin A and its specific downstream component activin receptor-like kinase 4 (ALK4) in stimulating fibrosis in non-cardiac organs...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28638997/follistatin-treatment-suppresses-serca1b-levels-independently-of-other-players-of-calcium-homeostasis-in-c2c12-myotubes
#6
János Fodor, Adrienn Gomba-Tóth, Tamás Oláh, János Almássy, Ernő Zádor, László Csernoch
Follistatin (FS) is a high affinity activin-binding protein, neutralizing the effects of the Transforming Growth Factor-beta (TGF-β) superfamily members, as myostatin (MSTN). Since MSTN emerged as a negative regulator, FS has been considered as a stimulator of skeletal muscle growth and differentiation. Here, we studied the effect of FS administration on the Ca(2+)-homeostasis of differentiating C2C12 skeletal muscle cells. FS-treatment increased the fusion index, the size of terminally differentiated myotubes, and transiently elevated the expression of the calcium-dependent protein phosphatase, calcineurin, at the beginning of differentiation...
June 21, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28632450/combinations-of-activin-a-or-nicotinamide-with-the-pancreatic-transcription-factor-pdx1-support-differentiation-of-human-amnion-epithelial-cells-toward-a-pancreatic-lineage
#7
Shruti Balaji, Yu Zhou, Emmanuel C Opara, Shay Soker
The differentiation of multipotent stem cells toward a pancreatic lineage provides us with an alternative cell-based therapeutic approach to type 1 diabetes and enables us to study pancreas development. The current study aims to study the effect of growth factors such as activin A or nicotinamide, alone and in combinations with the transcription factor, PDX1 (pancreatic and duodenal homeobox-1), on human amnion epithelial cells (hAECs) toward a pancreatic lineage. Ectopic expression of Pdx1 followed by treatment of hAECs with nicotinamide for 4 days resulted in strong induction of pancreatic endoderm and pancreatic progenitor genes, including NKX6...
June 20, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28632033/overexpression-of-alk5-induces-human-tenon-s-capsule-fibroblasts-transdifferentiation-and-fibrosis-in-vitro
#8
Shu-Hao Fu, Hui-Ying Wang, Jia-Ying Zhang, Hui-Min Shi, Nan Zhang, Wen Ye, Yi-Qin Xiao
PURPOSE: To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. METHODS: (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot...
February 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28629737/the-obligatory-role-of-activin-a-in-the-formation-of-heterotopic-bone-in-fibrodysplasia-ossificans-progressiva
#9
Dana M Alessi Wolken, Vincent Idone, Sarah J Hatsell, Paul B Yu, Aris N Economides
Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder that presents at birth with only minor patterning defects, but manifests its debilitating pathology early in life with episodic, yet progressive and cumulative, heterotopic ossification (HO) of ligaments, tendons, and a subset of major skeletal muscles. The resulting HO lesions are endochondral in nature, and appear to be linked to inflammatory stimuli arising in association with known injuries, or from inflammation linked to normal tissue repair...
June 16, 2017: Bone
https://www.readbyqxmd.com/read/28628913/age-dependent-effects-of-alk5-inhibition-and-mechanism-of-neuroprotection-in-neonatal-hypoxic-ischemic-brain-injury
#10
Brian H Kim, Mariano Guardia Clausi, Michelle Frondelli, Israel C Nnah, Chaitali Saqcena, Radek Dobrowolski, Steven W Levison
Neonatal encephalopathy due to hypoxic-ischemic (HI) brain injury triggers a wave of neuroinflammatory events attributed to causing the progressive degeneration and functional deficits seen weeks after the initial insult. In a recent set of studies, we evaluated the therapeutic efficacy of a small molecule antagonist for ALK5 (activin-like kinase 5 ), TGF-β receptor in a rat model of moderate perinatal HI and found significant improvements in neurologic outcomes. Here, we have extended those studies to evaluate the efficacy of delayed TGF-β receptor antagonism on postnatal day (P) 6 and P9 HI rat pups with and without hypothermia...
June 20, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28624955/presynaptic-inhibition-of-nociceptive-neurotransmission-by-somatosensory-neuron-secreted-suppressors
#11
REVIEW
Kaicheng Li, Bing Cai, Changlin Li, Xu Zhang
Noxious stimuli cause pain by activating cutaneous nociceptors. The Aδ- and C-fibers of dorsal root ganglion (DRG) neurons convey the nociceptive signals to the laminae I-II of spinal cord. In the dorsal horn of spinal cord, the excitatory afferent synaptic transmission is regulated by the inhibitory neurotransmitter γ-aminobutyric acid and modulators such as opioid peptides released from the spinal interneurons, and by serotonin, norepinepherine and dopamine from the descending inhibitory system. In contrast to the accumulated evidence for these central inhibitors and their neural circuits in the dorsal spinal cord, the knowledge about the endogenous suppressive mechanisms in nociceptive DRG neurons remains very limited...
June 15, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28620643/activin-biology-after-lung-transplantation
#12
Glen P Westall, Gregory I Snell, Monika Loskot, Bronwyn Levvey, Robyn O'Hehir, Mark P Hedger, David M de Kretser
BACKGROUND: Activins A and B, members of the TGF-β superfamily, are produced as part of the physiological response to tissue damage and the resulting proinflammatory response. Given that lung allograft reperfusion results in an inflammatory response, it is likely that the activins and their binding protein follistatin will form part of the regulatory response. There is a need to document the response of these proteins to allograft reperfusion to determine if there is a role for the use of follistatin to control the biological actions of the activins because some of these are potentially damaging...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28620148/cfc1-is-a-cancer-stemness-regulating-factor-in-neuroblastoma
#13
Koji Chikaraishi, Hisanori Takenobu, Ryuichi P Sugino, Kyosuke Mukae, Jesmin Akter, Masayuki Haruta, Masafumi Kurosumi, Takaho A Endo, Haruhiko Koseki, Naoki Shimojo, Miki Ohira, Takehiko Kamijo
BACKGROUND: Despite the use of aggressive therapy, survival rates among high-risk neuroblastoma (NB) patients remain poor. Cancer stem cells (CSCs) are considered to be critically involved in the recurrence and metastasis of NB and are isolated as NB spheres. METHODS: The gene expression profiling of adherent (control) and sphere-forming primary NB cells was conducted using a gene expression microarray. CFC1, which functions in the development of embryos and decides the left-right axis, was strongly expressed in sphere-forming cells only and was related to the unfavorable prognosis of NB patients...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28616035/neuroprotective-effects-of-activin-a-on-endoplasmic-reticulum-stress-mediated-apoptotic-and-autophagic-pc12-cell-death
#14
Long-Xing Xue, Hong-Yu Liu, Yang Cui, Yue Dong, Jiao-Qi Wang, Qiu-Ye Ji, Jin-Ting He, Min Yao, Ying-Ying Wang, Yan-Kun Shao, Jing Mang, Zhong-Xin Xu
Activin A, a member of the transforming growth factor-beta superfamily, plays a neuroprotective role in multiple neurological diseases. Endoplasmic reticulum (ER) stress-mediated apoptotic and autophagic cell death is implicated in a wide range of diseases, including cerebral ischemia and neurodegenerative diseases. Thapsigargin was used to induce PC12 cell death, and Activin A was used for intervention. Our results showed that Activin A significantly inhibited morphological changes in thapsigargin-induced apoptotic cells, and the expression of apoptosis-associated proteins [cleaved-caspase-12, C/EBP homologous protein (CHOP) and cleaved-caspase-3] and biomarkers of autophagy (Beclin-1 and light chain 3), and downregulated the expression of thapsigargin-induced ER stress-associated proteins [inositol requiring enzyme-1 (IRE1), tumor necrosis factor receptor-associated factor 2 (TRAF2), apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38]...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28612305/the-cardiovascular-effect-of-single-injection-and-toxicologic-effects-of-repetitive-2-week-intravenous-administration-of-activin-a-bmp-2-chimera-in-beagle-dog
#15
Jae Hyup Lee, Senyon Choe, Shihuan Han
This study was performed for the purpose to evaluate the effect of activin A/BMP-2 chimera (AB204) on cardiovascular system and toxicological effect in beagle dogs. When administered AB204 at the dose of 0.32 mg/kg via intravenous injection in beagle dogs, there were no changes in systolic, diastolic and mean blood pressure as well as in pulse rate, in addition that there were no differences in ORS complex, PR interval, R-R interval, QT interval and QTcV interval on the electrocardiography. Also, when administered AB204 at the doses of 0...
June 13, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28612286/placental-and-maternal-serum-activin-a-in-spontaneous-and-induced-labor-in-late-term-pregnancy
#16
L Funghi, M Torricelli, R Novembri, S Vannuccini, G Cevenini, M Di Tommaso, F M Severi, F Petraglia
PURPOSE: Feto-placental unit represents an important source of activin A, a member of transforming growth factors-β involved in the mechanisms of labor. No evidences are available on activin A in pregnancies beyond 41 weeks of gestation, where induction of labor is often required. The present study aimed to evaluate activin A maternal serum levels and placental mRNA expression in term and late-term pregnancy, with spontaneous or induced labor, and its possible role to predict the response to labor induction...
June 13, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28607086/specific-targeting-of-tgf-%C3%AE-family-ligands-demonstrates-distinct-roles-in-the-regulation-of-muscle-mass-in-health-and-disease
#17
Justin L Chen, Kelly L Walton, Adam Hagg, Timothy D Colgan, Katharine Johnson, Hongwei Qian, Paul Gregorevic, Craig A Harrison
The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs) encoding ligand-specific antagonists into the tibialis anterior (TA) muscles of C57BL/6 mice. Eight weeks after AAV injection, inhibition of activin A and activin B signaling produced moderate (∼20%), but significant, increases in TA mass, indicating that endogenous activins repress muscle growth...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28606101/international-physician-survey-on-management-of-fop-a-modified-delphi-study
#18
Maja Di Rocco, Genevieve Baujat, Marta Bertamino, Matthew Brown, Carmen L De Cunto, Patricia L R Delai, Elisabeth M W Eekhoff, Nobuhiko Haga, Edward Hsiao, Richard Keen, Rolf Morhart, Robert J Pignolo, Frederick S Kaplan
Fibrodysplasia ossificans progressiva (FOP), a disabling disorder of progressive heterotopic ossification (HEO), is caused by heterozygous gain-of- function mutations in Activin receptor A, type I (ACVR1, also known as ALK2), a bone morphogenetic protein (BMP) type I receptor. Presently, symptomatic management is possible, but no definitive treatments are available. Although extensive guidelines for symptomatic management are widely used, regional preferences exist. In order to understand if there was worldwide consensus among clinicians treating FOP patients, an expert panel of physicians directly involved in FOP patient care was convened...
June 12, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28605600/activin-and-bmp4-signaling-converge-on-wnt-activation-during-odontogenesis
#19
H-J E Kwon, S Jia, Y Lan, H Liu, R Jiang
Previous studies show that both activin and Bmp4 act as crucial mesenchymal odontogenic signals during early tooth development. Remarkably, mice lacking activin-βA ( Inhba(-/-)) and mice with neural crest-specific inactivation of Bmp4 ( Bmp4(ncko/ncko)) both exhibit bud-stage developmental arrest of the mandibular molar tooth germs while their maxillary molar tooth germs completed morphogenesis. In this study, we found that, whereas expression of Inhba and Bmp4 in the developing tooth mesenchyme is independent of each other, Bmp4(ncko/ncko)Inhba(-/-) compound mutant mice exhibit early developmental arrest of all tooth germs...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28595946/the-effects-of-pessimism-on-cell-mediated-immunity-in-rats
#20
Katarzyna Curzytek, Marta Kubera, Ewa Trojan, Kinga Wójcik, Agnieszka Basta-Kaim, Jan Detka, Michael Maes, Rafal Rygula
We used a recently developed ambiguous-cue interpretation (ACI) paradigm to investigate whether 'optimism' and 'pessimism' as behavioural traits may be interrelated with immune functions in rodents. To this aim, in a series of ACI tests (cognitive bias screening, CBS), we identified rats that displayed 'pessimistic' and 'optimistic' traits. We found significant differences in immune biomarkers between 'optimistic' and 'pessimistic' animals. Moreover 'pessimism' was associated with significantly lower relative weight of the spleen and thymus, significantly decreased proliferative activity of splenocytes...
June 5, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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