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Activin A

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https://www.readbyqxmd.com/read/28815607/a-3d-tri-culture-system-reveals-that-activin-receptor-like-kinase-5-and-connective-tissue-growth-factor-drive-human-glomerulosclerosis
#1
John P Waters, Yvonne C Richards, Jeremy N Skepper, Mark Southwood, Paul D Upton, Nicholas W Morrell, Jordan S Pober, John R Bradley
Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GEC), podocytes and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis...
August 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28798778/tumorigenic-and-differentiation-potentials-of-embryonic-stem-cells-depend-on-tgf%C3%AE-family-signaling-lessons-from-teratocarcinoma-cells-stimulated-to-differentiate-with-retinoic-acid
#2
Olga Gordeeva, Sergey Khaydukov
A significant challenge for the development of safe pluripotent stem cell-based therapies is the incomplete in vitro differentiation of the pluripotent stem cells and the presence of residual undifferentiated cells initiating teratoma development after transplantation in recipients. To understand the mechanisms of incomplete differentiation, a comparative study of retinoic acid-induced differentiation of mouse embryonic stem (ES) and teratocarcinoma (EC) cells was conducted. The present study identified differences in proliferative activity, differentiation, and tumorigenic potentials between ES and EC cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#3
Young-Chan Kwon, Reina Sasaki, Keith Meyer, Ranjit Ray
Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In our previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition state (EMT) and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of HCV core expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28782882/the-expansion-of-heterotopic-bone-in-fibrodysplasia-ossificans-progressiva-is-activin-a-dependent
#4
Jaymin Upadhyay, LiQin Xie, Lily Huang, Nanditha Das, Rachel C Stewart, Morgan C Lyon, Keryn Palmer, Saathyaki Rajamani, Chris Graul, Merryl Lobo, Tyler J Wellman, Edward J Soares, Matthew D Silva, Jacob Hesterman, Lili Wang, Xialing Wen, Xiaobing Qian, Kalyan Nannuru, Vincent Idone, Andrew J Murphy, Aris N Economides, Sarah J Hatsell
Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disorder that is characterized by episodic yet cumulative heterotopic ossification (HO) in skeletal muscles, tendons, and ligaments over a patient's lifetime. FOP is caused by missense mutations in the type I Bone Morphogenetic Protein (BMP) receptor ACVR1. We have determined that the formation of heterotopic bone in FOP requires activation of mutant ACVR1 by Activin A, in part by showing that prophylactic inhibition of Activin A blocks HO in a mouse model of FOP...
August 7, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28782519/identification-of-novel-alk2-inhibitors-and-their-effect-on-cancer-cells
#5
Minsung Kim, Okran Choi, Suhkneung Pyo, Sang Un Choi, Chi Hoon Park
Bone morphogenetic protein 9 (BMP9), a member of the TGF-β superfamily, is considered a regulator of glucose homeostasis as well as a neuronal differentiation factor. BMP9 induces phosphorylation of Smad1/5 through activin receptor-like kinase 1 and 2 (ALK1 and ALK2). Recently, many studies have shown that BMP9 contributes to tumorigenesis, and aberrant ALK2 expression is involved in many diseases. To investigate the role of BMP9-ALK2 signaling in cancer cells, we used TF-1 cells that require granulocyte-macrophage colony-stimulating factor (GM-CSF) for cell proliferation...
August 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28782045/nodal-activin-pathway-is-a-conserved-neural-induction-signal-in-chordates
#6
Yann Le Petillon, Guillaume Luxardi, Pierluigi Scerbo, Marie Cibois, Anthony Leon, Lucie Subirana, Manuel Irimia, Laurent Kodjabachian, Hector Escriva, Stephanie Bertrand
Neural induction is the process through which pluripotent cells are committed to a neural fate. This first step of Central Nervous System formation is triggered by the "Spemann organizer" in amphibians and by homologous embryonic regions in other vertebrates. Studies in classical vertebrate models have produced contrasting views about the molecular nature of neural inducers and no unifying scheme could be drawn. Moreover, how this process evolved in the chordate lineage remains an unresolved issue. In this work, by using graft and micromanipulation experiments, we definitively establish that the dorsal blastopore lip of the cephalochordate amphioxus is homologous to the vertebrate organizer and is able to trigger the formation of neural tissues in a host embryo...
August 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28781074/activin-signals-through-smad2-3-to-increase-photoreceptor-precursor-yield-during-embryonic-stem-cell-differentiation
#7
Amy Q Lu, Evgenya Y Popova, Colin J Barnstable
In vitro differentiation of mouse embryonic stem cells (ESCs) into retinal fates can be used to study the roles of exogenous factors acting through multiple signaling pathways during retina development. Application of activin A during a specific time frame that corresponds to early embryonic retinogenesis caused increased generation of CRX(+) photoreceptor precursors and decreased PAX6(+) retinal progenitor cells (RPCs). Following activin A treatment, SMAD2/3 was activated in RPCs and bound to promoter regions of key RPC and photoreceptor genes...
July 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28767427/mir-338-3p-inhibits-the-invasion-of-renal-cell-carcinoma-by-downregulation-of-alk5
#8
Xiaoqian Zhang, Chunxia Wang, Hui Li, Xiaobin Niu, Xinwei Liu, Dongxu Pei, Xiaolan Guo, Xiaona Xu, Yongwei Li
BACKGROUND: The current study aims to elucidate the role of miRNA-338-3p (miR-338-3p) in the invasion of renal cell carcinoma (RCC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-338-3p in human RCC cell lines with high metastatic potential (Caki-1) and low metastatic potential (786-O), respectively. The Caki-1 and 786-O cells were transfected with miR-338-3p mimic or inhibitor. Wound healing assay, Transwell assay and western blotting were performed to analyze the invasive ability and expression of activin receptor-like kinase 5 (ALK5) in the RCC cell lines...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765625/blood-testis-barrier-integrity-depends-on-pin1-expression-in-sertoli-cells
#9
Rabia Islam, Heein Yoon, Bong-Soo Kim, Han-Sol Bae, Hye-Rim Shin, Woo-Jin Kim, Won-Joon Yoon, Yun-Sil Lee, Kyung Mi Woo, Jeong-Hwa Baek, Hyun-Mo Ryoo
The conformation and function of a subset of serine and threonine-phosphorylated proteins are regulated by the prolyl isomerase Pin1 through isomerization of phosphorylated Ser/Thr-Pro bonds. Pin1 is intensely expressed in Sertoli cells, but its function in this post mitotic cell remains unclear. Our aim was to investigate the role of Pin1 in the Sertoli cells. Lack of Pin1 caused disruption of the blood-testis barrier. We next investigated if the activin pathways in the Sertoli cells were affected by lack of Pin1 through immunostaining for Smad3 protein in testis tissue...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28763624/comparative-transcriptomic-analysis-of-porcine-peripheral-blood-reveals-differentially-expressed-genes-from-the-cytokine-cytokine-receptor-interaction-pathway-related-to-health-status
#10
M H Ye, H Bao, Y Meng, L L Guan, P Stothard, G Plastow
While some research has looked into the host genetic response in pigs challenged with specific viruses or bacteria, few studies have explored the expression changes of transcripts in the peripheral blood of sick pigs which may be infected with multiple pathogens on farms. In this study, peripheral blood transcriptome architecture in 64 Duroc sired commercial pigs, including 18 healthy animals at entry to a growing facility (set as a control) and 23 pairs of samples from healthy and sick pen mates, was generated using RNA-Seq technology...
August 1, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28760345/dynamics-of-actinotrichia-regeneration-in-the-adult-zebrafish-fin
#11
Désirée König, Lionel Page, Bérénice Chassot, Anna Jaźwińska
The skeleton of adult zebrafish fins comprises lepidotrichia, which are dermal bones of the rays, and actinotrichia, which are non-mineralized spicules at the distal margin of the appendage. Little is known about the regenerative dynamics of the actinotrichia-specific structural proteins called Actinodins. Here, we used immunofluorescence analysis to determine the contribution of two paralogous Actinodin proteins, And1/2, in regenerating fins. Both proteins were detected in the secretory organelles in the mesenchymal cells of the blastema, but only And1 was detected in the epithelial cells of the wound epithelium...
July 29, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28760302/developmental-therapeutics-in-myeloproliferative-neoplasms
#12
REVIEW
Prithviraj Bose, Srdan Verstovsek
The unprecedented success of the Janus kinase (JAK) 1/2 inhibitor ruxolitinib in myelofibrosis (MF) provided much-needed impetus for clinical drug development for the Philadelphia chromosome-negative myeloproliferative neoplasms. The survival benefit conferred by this agent, along with its marked efficacy with regard to spleen volume and symptom reduction, have made ruxolitinib the cornerstone of drug therapy in MF. However, there remain significant unmet needs in the treatment of patients with MF, and many novel classes of agents continue to be investigated in efforts to build on the progress made with ruxolitinib...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28759733/protective-effect-of-rimonabant-a-canabinoid-receptor-1-antagonist-on-nonalcoholic-fatty-liver-disease-in-a-rat-model-by-modulating-the-hepatic-expression-of-activin-a-and-follistatin
#13
Noha Ibrahim Hussien, Hanan I El-Kerdasy, Mohamed El-Tantawy Ibrahim
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality with no proven effective therapy yet. Endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. The present study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced by choline deficient (CD) diet in rats, as well as to detect whether it can modulate the hepatic expression of activin A and follistatin or not...
July 31, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28758906/activin-a-enhances-mtor-signaling-to-promote-aberrant-chondrogenesis-in-fibrodysplasia-ossificans-progressiva
#14
Kyosuke Hino, Kazuhiko Horigome, Megumi Nishio, Shingo Komura, Sanae Nagata, Chengzhu Zhao, Yonghui Jin, Koichi Kawakami, Yasuhiro Yamada, Akira Ohta, Junya Toguchida, Makoto Ikeya
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed...
July 31, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28754575/heterotopic-bone-induction-via-bmp-signaling-potential-therapeutic-targets-for-fibrodysplasia-ossificans-progressiva
#15
Takenobu Katagiri, Sho Tsukamoto, Mai Kuratani
More than 50years ago, Marshal M. Urist detected "heterotopic bone-inducing activity" in demineralized bone matrix. This unique activity was referred to as "bone morphogenetic protein (BMP)" because it was sensitive to trypsin digestion. Purification of the bone-inducing activity from demineralized bone matrix using a bone-inducing assay in vivo indicated that the original "BMP" consisted of a mixture of new members of the transforming growth factor-β (TGF-β) family. The establishment of new in vitro assay systems that reflect the bone-inducing activity of BMPs in vivo have revealed the functional receptors and downstream effectors of BMPs...
July 25, 2017: Bone
https://www.readbyqxmd.com/read/28751863/bone-morphogenetic-protein-9-protects-against-neonatal-hyperoxia-induced-impairment-of-alveolarization-and-pulmonary-inflammation
#16
Xueyu Chen, Mar Orriols, Frans J Walther, El Houari Laghmani, Annemarie M Hoogeboom, Anne C B Hogen-Esch, Pieter S Hiemstra, Gert Folkerts, Marie-José T H Goumans, Peter Ten Dijke, Nicholas W Morrell, Gerry T M Wagenaar
Aim: Effective treatment of premature infants with bronchopulmonary dysplasia (BPD) is lacking. We hypothesize that bone morphogenetic protein 9 (BMP9), a ligand of the TGF-β family that binds to the activin receptor-like kinase 1 (ALK1)-BMP receptor type 2 (BMPR2) receptor complex, may be a novel therapeutic option for BPD. Therefore, we investigated the cardiopulmonary effects of BMP9 in neonatal Wistar rats with hyperoxia-induced BPD. Methods: Directly after birth Wistar rat pups were exposed to 100% oxygen for 10 days...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28748922/regulation-of-drosophila-hematopoietic-sites-by-activin-%C3%AE-from-active-sensory-neurons
#17
Kalpana Makhijani, Brandy Alexander, Deepti Rao, Sophia Petraki, Leire Herboso, Katelyn Kukar, Itrat Batool, Stephanie Wachner, Katrina S Gold, Corinna Wong, Michael B O'Connor, Katja Brückner
An outstanding question in animal development, tissue homeostasis and disease is how cell populations adapt to sensory inputs. During Drosophila larval development, hematopoietic sites are in direct contact with sensory neuron clusters of the peripheral nervous system (PNS), and blood cells (hemocytes) require the PNS for their survival and recruitment to these microenvironments, known as Hematopoietic Pockets. Here we report that Activin-β, a TGF-β family ligand, is expressed by sensory neurons of the PNS and regulates the proliferation and adhesion of hemocytes...
July 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28747082/construction-of-functional-pancreatic-artificial-islet-tissue-composed-of-fibroblast-modified-polylactic-co-glycolic-acid-membrane-and-pancreatic-stem-cells
#18
Liping Liu, Jing Tan, Baoyuan Li, Qian Xie, Junwen Sun, Hongli Pu, Li Zhang
Objective To improve the biocompatibility between polylactic- co-glycolic acid membrane and pancreatic stem cells, rat fibroblasts were used to modify the polylactic- co-glycolic acid membrane. Meanwhile, we constructed artificial islet tissue by compound culturing the pancreatic stem cells and the fibroblast-modified polylactic- co-glycolic acid membrane and explored the function of artificial islets in diabetic nude mice. Methods Pancreatic stem cells were cultured on the fibroblast-modified polylactic- co-glycolic acid membrane in dulbecco's modified eagle medium containing activin-A, β-catenin, and exendin-4...
January 1, 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28738706/relationship-between-premature-brain-injury-and-multiple-biomarkers-in-cord-blood-and-amniotic-fluid
#19
Hongyan Lu, Weiling Huang, Xiaoqing Chen, Qiuxia Wang, Qiang Zhang, Ming Chang
PURPOSE: To investigate the relationship between premature brain injury and multiple biomarkers in cord blood and amniotic fluid, identify potential biomarkers for early monitoring of premature brain injury. METHODS: 130 cases of singleton premature infants with gestational age less than 34 weeks were evaluated. Based on brain imaging examination, all cases were divided into brain injury group and no brain injury group. Eleven biomarkers in cord blood and amniotic fluid were measured...
July 24, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28737766/endothelial-fibrosis-induced-by-suppressed-stat3-expression-mediated-by-signaling-involving-the-tgf-%C3%AE-1-alk5-smad-pathway
#20
Alvaro Becerra, Macarena Rojas, Alejandro Vallejos, Vicente Villegas, Lorena Pérez, Claudio Cabello-Verrugio, Felipe Simon
During systemic inflammatory pathologies, mediators of inflammation circulate in the bloodstream and interact with endothelial cells (ECs), resulting in endothelial dysfunction that maintains and enhances the pathological condition. Inflammatory mediators change the protein expression profile of ECs, which become activated fibroblasts via endothelial-to-mesenchymal transition. This process is characterized by downregulated endothelial proteins and strongly upregulated fibrotic-specific genes and extracellular matrix-forming proteins...
July 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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