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Follistatin

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https://www.readbyqxmd.com/read/29330193/structure-of-the-human-myostatin-precursor-and-determinants-of-growth-factor-latency
#1
Thomas R Cotton, Gerhard Fischer, Xuelu Wang, Jason C McCoy, Magdalena Czepnik, Thomas B Thompson, Marko Hyvönen
Myostatin, a key regulator of muscle mass in vertebrates, is biosynthesised as a latent precursor in muscle and is activated by sequential proteolysis of the pro-domain. To investigate the molecular mechanism by which pro-myostatin remains latent, we have determined the structure of unprocessed pro-myostatin and analysed the properties of the protein in its different forms. Crystal structures and SAXS analyses show that pro-myostatin adopts an open, V-shaped structure with a domain-swapped arrangement. The pro-mature complex, after cleavage of the furin site, has significantly reduced activity compared with the mature growth factor and persists as a stable complex that is resistant to the natural antagonist follistatin...
January 12, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29317401/acute-and-chronic-increases-of-circulating-fstl1-normalize-energy-substrate-metabolism-in-pacing-induced-heart-failure
#2
Mitsuru Seki, Jeffery C Powers, Sonomi Maruyama, Maria A Zuriaga, Chia-Ling Wu, Clara Kurishima, Lydia Kim, Jesse Johnson, Anthony Poidomani, Tao Wang, Eric Muñoz, Sudarsan Rajan, Joon Y Park, Kenneth Walsh, Fabio A Recchia
BACKGROUND: FSTL1 (follistatin-like protein 1) is an emerging cardiokine/myokine that is upregulated in heart failure (HF) and is found to be cardioprotective in animal models of cardiac injury. We tested the hypothesis that circulating FSTL1 can affect cardiac function and metabolism under baseline physiological conditions and in HF. METHODS AND RESULTS: FSTL1 was acutely (10 minutes) or chronically (2 weeks) infused to attain clinically relevant blood levels in conscious dogs with cardiac tachypacing-induced HF...
January 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29310676/functional-role-of-akt-signaling-in-bovine-early-embryonic-development-potential-link-to-embryotrophic-actions-of-follistatin
#3
Mohamed Ashry, Sandeep K Rajput, Joseph K Folger, Jason G Knott, Nabil A Hemeida, Omaima M Kandil, Refaat S Ragab, George W Smith
BACKGROUND: TGF-β signaling pathways regulate several crucial processes in female reproduction. AKT is a non-SMAD signaling pathway regulated by TGF-β ligands essential for oocyte maturation and early embryonic development in the mouse, but its regulatory role in bovine early embryonic development is not well established. Previously, we demonstrated a stimulatory role for follistatin (a binding protein for specific members of TGF-β superfamily) in early bovine embryonic development...
January 8, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29288571/early-second-trimester-maternal-serum-markers-in-prediction-of-gestational-diabetes-mellitus
#4
Baihui Zhao, Xiujun Han, Qing Meng, Qiong Luo
AIMS: To determine whether maternal serum markers in the early-second trimester are useful for prediction of gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 876 singleton pregnancies were recruited in the present study. Blood samples were collected during 16-20 gestational weeks. GDM women were diagnosed by OGTT during 24-28 gestational weeks. Fifty-six cases of GDM and 73 healthy cases were selected. Maternal serum concentrations of placental protein 13 (PP13), pentraxin 3 (PTX3), soluble fms-like tyrosine kinase-1 (sFlt-1), myostatin and follistatin (FST) were detected at 16-20 weeks' gestation...
December 29, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29287776/activin-a-causes-hepatic-stellate-cell-activation-via-the-induction-of-tnf%C3%AE-%C3%AE%C2%BA%C3%AE-%C3%AE-tgf%C3%AE-in-kupffer-cells
#5
Foteini Kiagiadaki, Marilena Kampa, Argyro Voumvouraki, Elias Castanas, Elias Kouroumalis, George Notas
Background&Aims. TGFβ superfamily member Activin-A is a multifunctional hormone/cytokine expressed in multiple tissues and cells., where it regulates cellular differentiation, proliferation, inflammation and tissue architecture. High activin-A levels have been reported in alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH). Our aim was to identify the cell types involved in the fibrotic processes induced by activin-A in liver and verify the liver diseases that this molecule can be found increased...
December 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29281176/the-impact-of-the-glomerular-filtration-rate-on-the-human-plasma-proteome
#6
Anders Christensson, Jessica A Ash, Robert K DeLisle, Fraser W Gaspar, Rachel Ostroff, Anders Grubb, Veronica Lindström, Laila Bruun, Steve A Williams
PURPOSE: The application of proteomics in chronic kidney disease (CKD) can potentially uncover biomarkers and pathways that are predictive of disease. EXPERIMENTAL DESIGN: Within this context, this study examined the relationship between the human plasma proteome and glomerular filtration rate (GFR) as measured by iohexol clearance in a cohort from Sweden (N = 389; GFR range: 8 - 100 mL/min/1.73m2 ). A total of 2893 proteins were quantified using a modified aptamer assay...
December 27, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29246685/silica-nanoparticle-releases-sirt6-induced-epigenetic-silencing-of-follistatin
#7
Lingda Zhang, Bing Han, Jie Xiang, Kangli Liu, Haojie Dong, Xiangwei Gao
Follistatin (FST) plays a protective role during silica nanoparticle (SiO2 NP) exposure. SiO2 NP treatment induces FST transcription with an unknown mechanism. We herein reported that SIRT6, one of the sirtuin family members, induced epigenetic silencing of FST. The expression of FST was elevated after SIRT6 knockdown while reduced after SIRT6 overexpression. Chromatin immunoprecipitation revealed a direct interaction between SIRT6 with FST promoter. Knockdown of SIRT6 increased both Ac-H3K9 level and Ac-H3K56 level at FST promoter region...
December 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29220580/the-influence-of-adiposity-and-acute-exercise-on-circulating-hepatokines-in-normal-weight-and-overweight-obese-men
#8
Jack A Sargeant, Guruprasad P Aithal, Toshinari Takamura, Hirofumi Misu, Hiroaki Takayama, Jessica A Douglas, Mark C Turner, David J Stensel, Myra A Nimmo, David R Webb, Thomas Yates, James A King
Hepatokines are liver-secreted proteins with potential to influence glucose regulation and other metabolic parameters. This study investigated differences in adiposity status on five novel hepatokines and characterised their response to acute moderate-intensity exercise in groups of normal weight and overweight/obese men. Twenty-two men were recruited into normal weight and overweight/obese groups (BMI: 18.5 to 24.9 and 25.0 to 34.9 kg∙m<sup>-2</sup>). Each completed two experimental trials, exercise and control...
December 8, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29212066/fstl1-promotes-glioma-growth-through-the-bmp4-smad1-5-8-signaling-pathway
#9
Xin Jin, Er Nie, Xu Zhou, Ailiang Zeng, Tianfu Yu, Tongle Zhi, Kuan Jiang, Yingyi Wang, Junxia Zhang, Yongping You
BACKGROUND: Gliomas result in the highest morbidity and mortality rates of intracranial primary central nervous system tumors because of their aggressive growth characteristics and high postoperative recurrence. They are characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior in patients. Proliferation is a key aspect of the clinical progression of malignant gliomas, complicating complete surgical resection and enabling tumor regrowth and further proliferation of the surviving tumor cells...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29192144/downregulation-of-myostatin-pathway-in-neuromuscular-diseases-may-explain-challenges-of-anti-myostatin-therapeutic-approaches
#10
Virginie Mariot, Romain Joubert, Christophe Hourdé, Léonard Féasson, Michael Hanna, Francesco Muntoni, Thierry Maisonobe, Laurent Servais, Caroline Bogni, Rozen Le Panse, Olivier Benvensite, Tanya Stojkovic, Pedro M Machado, Thomas Voit, Ana Buj-Bello, Julie Dumonceaux
Muscular dystrophies are characterized by weakness and wasting of skeletal muscle tissues. Several drugs targeting the myostatin pathway have been used in clinical trials to increase muscle mass and function but most showed limited efficacy. Here we show that the expression of components of the myostatin signaling pathway is downregulated in muscle wasting or atrophying diseases, with a decrease of myostatin and activin receptor, and an increase of the myostatin antagonist, follistatin. We also provide in vivo evidence in the congenital myotubular myopathy mouse model (knock-out for the myotubularin coding gene Mtm1) that a down-regulated myostatin pathway can be reactivated by correcting the underlying gene defect...
November 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/29180105/sex-hormone-binding-globulin-b-expression-in-the-rainbow-trout-ovary-prior-to-sex-differentiation
#11
Claudio Pérez, Cristian Araneda, Francisco Estay, Nelson F Díaz, Denise Vizziano-Cantonnet
Salmonids have two sex hormone-binding globulin (Shbg) paralogs. Shbga is mainly expressed in the liver, while Shbgb is secreted by the granulosa cells of the rainbow trout ovary. Coexpression of shbgb and the gonadal aromatase cyp19a1a mRNAs been observed in granulosa cells, suggesting a physiological coordination between Shbgb expression and estrogen synthesis. As estrogens are essential for female sex determination in the fish ovary, we propose that Shbgb participates in early ovarian differentiation, either by binding with estrogen or through another mechanism that remains to be discovered...
November 24, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29170109/activin-a-amplifies-dysregulated-bmp-signaling-and-induces-chondro-osseous-differentiation-of-primary-connective-tissue-progenitor-cells-in-patients-with-fibrodysplasia-ossificans-progressiva-fop
#12
REVIEW
Haitao Wang, Eileen M Shore, Robert J Pignolo, Frederick S Kaplan
BACKGROUND: Fibrodysplasia ossificans progressiva (FOP), is caused by mutations in the type I BMP receptor ACVR1 that lead to increased activation of the BMP-pSmad1/5/8 signaling pathway. Recent findings suggest that Activin A (Act A) promiscuously stimulates the bone morphogenetic protein (BMP) signaling pathway in vitro and mediates heterotopic ossification (HO) in mouse models of FOP, but primary data from FOP patient cells are lacking. OBJECTIVE: To examine BMP-pSmad1/5/8 pathway signaling and chondro-osseous differentiation in response to endogenous and exogenous Act A in primary connective tissue progenitor cells [CTPCs; also known as stem cells from human exfoliated deciduous teeth (SHED) cells] from patients with FOP...
November 20, 2017: Bone
https://www.readbyqxmd.com/read/29159199/dna-mediated-gene-therapy-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2b
#13
Julia Ma, Christophe Pichavant, Haley du Bois, Mital Bhakta, Michele P Calos
Mutations in the gene for dysferlin cause a degenerative disorder of skeletal muscle known as limb girdle muscular dystrophy 2B. To achieve gene delivery of plasmids encoding dysferlin to hind limb muscles of dysferlin knockout mice, we used a vascular injection method that perfused naked plasmid DNA into all major muscle groups of the hind limb. We monitored delivery by luciferase live imaging and western blot, confirming strong dysferlin expression that persisted over the 3-month time course of the experiment...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29156385/interaction-with-the-gdf8-11-pathway-reveals-treatment-options-for-adenocarcinoma-of-the-breast
#14
Christoph Wallner, Marius Drysch, Mustafa Becerikli, Henriette Jaurich, Johannes Maximilian Wagner, Stephanie Dittfeld, Julia Nagler, Kamran Harati, Mehran Dadras, Stathis Philippou, Marcus Lehnhardt, Björn Behr
Breast adenocarcinoma continues to be the most frequently diagnosed tumor entity. Despite established therapy options, mortality for breast cancer remains to be as high as 40,000 patients in the US annually. Thus, a need to develop a patient-oriented, targeted therapy exists. In this study, we investigated the interaction of breast adenocarcinoma with the ubiquitously present protein Follistatin and subsequently the GDF8/11 pathway. We analyzed primary histological samples from adenocarcinoma patients for expression of Follistatin and GDF8/11...
November 17, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29149247/quantitative-proteomic-profiling-of-bovine-follicular-fluid-during-follicle-development
#15
Rodrigo de Andrade Ferrazza, Elizabeth Moreira Dos Santos Schmidt, Monika Mihm Carmichael, Fabiana Ferreira de Souza, Richard Burchmore, Roberto Sartori, Peter David Eckersall, João Carlos Pinheiro Ferreira
Bovine follicular fluid (FF) constitutes the microenvironment of follicles and includes various biologically active proteins. We performed a study involving 18 healthy non-lactating Holstein cows to determine the protein expression profile of FF at key-stages of follicular development. Follicles were individually aspirated in vivo at pre-deviation (F1∼7.0mm); deviation (F1∼8.5mm); post-deviation (F1∼12.0mm); and pre-ovulatory stages of follicle development, which were confirmed by measurement of follicular estradiol and progesterone concentrations...
November 15, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29135371/follistatin-like-protein-1-upregulates-dendritic-cell-based-immunity-in-patients-with-nasopharyngeal-carcinoma
#16
Hong Wang, Shiping Huang, Senyong Wu, Shaolin Yin, Anzhou Tang, Wensheng Wen
Follistatin-like protein-1 (FSTL1) is an inflammatory factor that can induce an inflammatory response and is expressed in cancers. However, little is known about its content and function in nasopharyngeal carcinoma (NPC). Interleukin (IL)-12 and IL-4 are primarily secreted by dendritic cells (DCs) and activated T lymphocytes, respectively; these factors can induce Th cell differentiation and cytotoxic lymphocyte production, both of which facilitate tumors through the STAT4 and STAT6 pathways, respectively. In this study, the relationship between FSTL1 and both IL-12 and IL-4 as well as the functional mechanism of these cytokines was explored...
November 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29134682/differential-effects-of-follistatin-on-porcine-oocyte-competence-and-cumulus-cell-gene-expression-in-vitro
#17
Z Guo, M S Islam, D Liu, G Liu, L Lv, Y Yang, B Fu, L Wang, Z Liu, H He, H Wu
Several oocyte-derived genes/proteins are essential to early embryonic development. The expression and stability of these proteins are influenced by the autocrine/paracrine activity of factors released by oocytes and cumulus cells. This study investigated the paracrine and autocrine activity of follistatin (FS), which is secreted by oocytes and cumulus cells as part of porcine embryogenesis. Immunohistochemical (IHC) localization of follistatin was conducted on 100 randomly selected early- and late-cleaving two-cell embryos...
November 14, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29126163/identification-of-novel-cancer-biomarkers-of-prognostic-value-using-specific-gene-regulatory-networks-grn-a-novel-role-of-rad51ap1-for-ovarian-and-lung-cancers
#18
Dimple Chudasama, Valeria Bo, Marcia Hall, Vladimir Anikin, Jeyarooban Jeyaneethi, Jane Gregory, George Pados, Allan Tucker, Amanda Harvey, Ryan Pink, Emmanouil Karteris
To date, microarray analyses have led to the discovery of numerous individual "molecular signatures" associated with specific cancers. However, there are serious limitations for the adoption of these multi-gene signatures in the clinical environment for diagnostic or prognostic testing as studies with more power need to be carried out. This may involve larger richer cohorts and more advanced analyses.In this study, we conduct analyses -based on GRN- to reveal distinct and common biomarkers across cancer types...
November 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29123487/hypertrophy-stimulation-at-the-onset-of-type-i-diabetes-maintains-the-soleus-but-not-the-edl-muscle-mass-in-wistar-rats
#19
Marco A S Fortes, Maria V M Scervino, Gabriel N Marzuca-Nassr, Kaio F Vitzel, Carlos H da Justa Pinheiro, Rui Curi
Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus) or glycolytic (EDL) muscles...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29119699/effect-of-follistatin-on-pre-implantational-development-of-pig-parthenogenetic-embryos
#20
Yunsheng Li, Xing Liu, Zhen Chen, Dandan Song, Jie Yang, Xiaoyuan Zuo, Zubing Cao, Ya Liu, Yunhai Zhang
The present study was designed to explore effects of follistatin (FST) on pre-implantational development of parthenogenetically activated embryos (PAEs) in pigs. First, we investigated the FST messenger RNA expression level and dynamic FST protein expression patterns in porcine oocytes and PAEs. Then, PAEs were placed in embryo culture medium supplemented with 10 ng/mL of FST-288, FST-300, and FST-315. Next, PAEs were cultured with 0, 1, 10 and 100 ng/mL of FST-315 protein throughout the in vitro culture (IVC) duration...
November 9, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
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