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Activin A

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https://www.readbyqxmd.com/read/28443351/current-and-future-chemical-therapies-for-treating-anaemia-in-chronic-kidney-disease
#1
Francesco Locatelli, Lucia Del Vecchio, Maria Carmen Luise
Erythropoiesis-stimulating agents (ESAs) are not perfect, since they have potential side effects. Iron therapy is also receiving growing attention in recent years. Areas covered: We performed a literature search on PubMed using the following key words: anaemia, chronic kidney disease, HIF stabilisers, sotatercept, actin traps, iron, iron-containing phosphate binders, iron dialysate. We reviewed new drugs that are under clinical development to obtain better safety and activity and/or easier and cheaper manufacturing processes in comparison to available ESAs...
April 26, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28440452/bambi-overexpression-together-with-%C3%AE-sitosterol-ameliorates-nsclc-via-inhibiting-autophagy-and-inactivating-tgf-%C3%AE-smad2-3-pathway
#2
Xingchun Wang, Minjie Li, Mengyao Hu, Ping Wei, Wei Zhu
Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis. The BMP and activin receptor membrane bound inhibitor (BAMBI) has been identified as a hallmark of NSCLC and β-sitosterol possesses antitumor potentiality. This study explores the effect of BAMBI overexpression and β-sitosterol in the context of NSCLC. The results revealed that the transfection of pcDNA‑BAMBI and β-sitosterol treatment significantly reduced the levels of autophagy markers light chain 3 (LC3) II and Beclin 1, whereas the levels of LC3 I and p62 were promoted...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28432277/transforming-growth-factor-%C3%AE-1-promotes-invasion-of-human-jeg-3-trophoblast-cells-via-tgf-%C3%AE-smad3-signaling-pathway
#3
Zhongying Huang, Shangwei Li, Wei Fan, Qianhong Ma
Transforming growth factor (TGF)-β1 is involved invasion of human trophoblasts. However, the underlying mechanisms remain unclear. In this study, we performed Transwell assay and found that TGF-β1 promoted the invasion of trophoblast cell line JEG-3. Treatment with TGF-β1 up-regulated the expression of receptor-regulated Smad transcription factors Smad2 and Smad3, and two invasive-associated genes, namely, matrix metallopeptidase (MMP)-9 and MMP-2, in JEG-3 cells. Over-expressing activin receptor-like kinase (ALK) 5, the TGF-β type I receptor (TβRI) enhanced the up-regulation of Smad2, Smad3, MMP-9, and MMP-2 induced by TGF-β1, whereas application of TβRI inhibitor SB431542 diminished the stimulatory effects of TGF-β1 on these genes...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427897/boosters-and-barriers-for-direct-cardiac-reprogramming
#4
REVIEW
Mahmood Talkhabi, Elmira Rezaei Zonooz, Hossein Baharvand
Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs...
April 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28425077/unexpected-and-striking-effect-of-heparin-free-dialysis-on-cytokine-release
#5
Alicja Rydzewska-Rosolowska, Joanna Gozdzikiewicz-Lapinska, Jacek Borawski, Ewa Koc-Zorawska, Michal Mysliwiec, Beata Naumnik
Heparin (both unfractionated and low molecular weight) is not only a potent anticoagulant but also has many pleiotropic effects, some of which are mediated by cytokine release. We compared the effect of hemodialysis (HD) with enoxaparin as an anticoagulant and without systemic anticoagulation (heparin-grafted membrane-Evodial) on the release of monocyte chemoattractant protein 1 (MCP-1), endostatin (ES) and activin A (Act-A). Nineteen stable HD patients were dialyzed with or without heparin, and plasma levels of MCP-1, ES and Act-A were measured after such a dialysis...
April 19, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28424263/the-kielin-chordin-like-protein-kcp-attenuates-high-fat-diet-induced-obesity-and-metabolic-syndrome-in-mice
#6
Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-beta superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The Kielin/chordin-like Protein (KCP) is a secreted regulator of the TGF-beta superfamily pathways that can inhibit both TGF-beta and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
April 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28418896/nfkb-is-essential-for-activin-induced-colorectal-cancer-migration-via-upregulation-of-pi3k-mdm2-pathway
#7
Arundhati Jana, Nancy L Krett, Grace Guzman, Ahmer Khalid, Ozkan Ozden, Jonas J Staudacher, Jessica Bauer, Seung Hyun Baik, Timothy Carroll, Cemal Yazici, Barbara Jung
Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate the mechanism of metastatic activin signaling, we examined activated NFkB signaling and activin ligand expression in CRC patient samples and found a strong correlation...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412737/whole-exome-sequencing-identifies-sgcd-and-acvrl1-mutations-associated-with-total-anomalous-pulmonary-venous-return-tapvr-in-chinese-population
#8
Jun Li, Shiwei Yang, Zhening Pu, Juncheng Dai, Tao Jiang, Fangzhi Du, Zhu Jiang, Yue Cheng, Genyin Dai, Jun Wang, Jirong Qi, Liming Cao, Xueying Cheng, Cong Ren, Xinli Li, Yuming Qin
As a rare type of Congenital Heart Defects (CHD), the genetic mechanism of Total Anomalous Pulmonary Venous Return (TAPVR) remains unknown, although previous studies have revealed potential disease-driving regions/genes. Blood samples collected from the 6 sporadic TAPVR cases and 81 non-TAPVR controls were subjected to whole exome sequencing. All detected variations were confirmed by direct Sanger sequencing. Here, we identified 2 non-synonymous missense mutations: c.C652T, p.R218W in activin A receptor type II-like 1 (ACVRL1), c...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396222/activin-b-regulates-adipose-derived-mesenchymal-stem-cells-to-promote-skin-wound-healing-via-activation-of-the-mapk-signaling-pathway
#9
Lei Zhang, Pengcheng Xu, Xueer Wang, Min Zhang, Yuan Yan, Yinghua Chen, Lu Zhang, Lin Zhang
Adipose-derived stem cells (ADSCs) are multipotent stromal cells that can differentiate into a variety of cell types, including skin cells, and they can provide an abundant source of cells for skin tissue engineering and skin wound healing. The purpose of this study is to explore the therapeutic effects of activin B in combination with ADSCs and the possible signaling mechanism. In this study, we found that activin B was able to promote ADSC migration by inducing actin stress fiber formation in vitro. In vivo, activin B in combination with ADSCs was capable of enhancing α-SMA expression and wound closure...
April 8, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28387157/bone-morphogenetic-protein-9-increases-the-functional-expression-of-organic-anion-transporting-polypeptide-1a4-at-the-blood-brain-barrier-via-the-activin-receptor-like-kinase-1-receptor
#10
Wazir Abdullahi, Hrvoje Brzica, Kathryn Ibbotson, Thomas P Davis, Patrick T Ronaldson
Targeting uptake transporters such as organic anion transporting polypeptide 1a4 (Oatp1a4) at the blood-brain barrier (BBB) can facilitate central nervous system (CNS) drug delivery. Effective blood-to-brain drug transport via this strategy requires characterization of mechanisms that modulate BBB transporter expression and/or activity. Here, we show that activation of activin receptor-like kinase (ALK)-1 using bone morphogenetic protein (BMP)-9 increases Oatp1a4 protein expression in rat brain microvessels in vivo...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28363632/regional-localization-of-activin-%C3%AE-a-activin-%C3%AE-c-follistatin-proliferation-and-apoptosis-in-adult-and-developing-mouse-prostate-ducts
#11
Elspeth Gold, Sylvia Zellhuber-McMillan, Gail Risbridger, Francesco Elia Marino
Activins and inhibins, members of the TGF-β superfamily, are growth and differentiation factors involved in the regulation of several biological processes, including reproduction, development, and fertility. Previous studies have shown that the activin-βA subunit plays a pivotal role in prostate development. Activin-A inhibits branching morphogenesis in the developing prostate, and its expression is associated with increased apoptosis in the adult prostate. Follistatin, a structurally unrelated protein to activins, is an antagonist of activin-A...
January 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28362406/efficient-differentiation-of-pluripotent-stem-cells-to-nkx6-1-pancreatic-progenitors
#12
Emily C McGaugh, M Cristina Nostro
Pluripotent stem cells have the ability to self renew and differentiate to multiple lineages, making them an attractive source for the generation of pancreatic progenitor cells that can be used for the study of and future treatment of diabetes. This article outlines a four-stage differentiation protocol designed to generate pancreatic progenitor cells from human embryonic stem cells (hESCs). This protocol can be applied to a number of human pluripotent stem cell (hPSC) lines. The approach taken to generate pancreatic progenitor cells is to differentiate hESCs to accurately model key stages of pancreatic development...
March 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28362386/in-vitro-differentiation-of-human-pluripotent-stem-cells-into-trophoblastic-cells
#13
Jianle Wang, Montserrat C Anguera
The placenta is the first organ to develop during embryogenesis and is required for the survival of the developing embryo. The placenta is comprised of various trophoblastic cells that differentiate from the extra-embryonic trophectoderm cells of the preimplantation blastocyst. As such, our understanding of the early differentiation events of the human placenta is limited because of ethical and legal restrictions on the isolation and manipulation of human embryogenesis. Human pluripotent stem cells (hPSCs) are a robust model system for investigating human development and can also be differentiated in vitro into trophoblastic cells that express markers of the various trophoblast cell types...
March 16, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28361317/generation-of-gastrointestinal-organoids-from-human-pluripotent-stem-cells
#14
Jorge O Múnera, James M Wells
Over the past several decades, developmental biologists have discovered fundamental mechanisms by which organs form in developing embryos. With this information it is now possible to generate human "organoids" by the stepwise differentiation of human pluripotent stem cells using a process that recapitulates organ development. For the gastrointestinal tract, one of the first key steps is the formation of definitive endoderm and mesoderm, a process that relies on the TGFb molecule Nodal. Endoderm is then patterned along the anterior-posterior axis, with anterior endoderm forming the foregut and posterior endoderm forming the mid and hindgut...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28359790/design-synthesis-and-optimization-of-7-substituted-pyrazolo-4-3-b-pyridine-alk5-activin-receptor-like-kinase-5-inhibitors
#15
Mark Sabat, Haixia Wang, Nick Scorah, J David Lawson, Joy Atienza, Ruhi Kamran, Mark S Hixon, Douglas R Dougan
A series of potent ALK5 inhibitors were designed using a SBDD approach and subsequently optimized to improve drug likeness. Starting with a 4-substituted quinoline screening hit, SAR was conducted using a ALK5 binding model to understand the binding site and optimize activity. The resulting inhibitors displayed excellent potency but were limited by high in vitro clearance in rat and human microsomes. Using a scaffold morphing strategy, these analogs were transformed into a related pyrazolo[4,3-b]pyridine series with improved ADME properties...
May 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28352232/dickkopf-3-upregulates-vegf-in-cultured-human-endothelial-cells-by-activating-activin-receptor-like-kinase-1-alk1-pathway
#16
Carla L Busceti, Simona Marchitti, Franca Bianchi, Paola Di Pietro, Barbara Riozzi, Rosita Stanzione, Milena Cannella, Giuseppe Battaglia, Valeria Bruno, Massimo Volpe, Francesco Fornai, Ferdinando Nicoletti, Speranza Rubattu
Dkk-3 is a member of the dickkopf protein family of secreted inhibitors of the Wnt pathway, which has been shown to enhance angiogenesis. The mechanism underlying this effect is currently unknown. Here, we used cultured HUVECs to study the involvement of the TGF-β and VEGF on the angiogenic effect of Dkk-3. Addition of hrDkk-3 peptide (1 or 10 ng/ml) to HUVECs for 6 or 12 h enhanced the intracellular and extracellular VEGF protein levels, as assessed by RTPCR, immunoblotting, immunocytochemistry and ELISA...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28348240/endothelial-transcription-factor-klf2-negatively-regulates-liver-regeneration-via-induction-of-activin-a
#17
Yosif Manavski, Tobias Abel, Junhao Hu, Dina Kleinlützum, Christian J Buchholz, Christina Belz, Hellmut G Augustin, Reinier A Boon, Stefanie Dimmeler
Endothelial cells (ECs) not only are important for oxygen delivery but also act as a paracrine source for signals that determine the balance between tissue regeneration and fibrosis. Here we show that genetic inactivation of flow-induced transcription factor Krüppel-like factor 2 (KLF2) in ECs results in reduced liver damage and augmentation of hepatocyte proliferation after chronic liver injury by treatment with carbon tetrachloride (CCl4). Serum levels of GLDH3 and ALT were significantly reduced in CCl4-treated EC-specific KLF2-deficient mice...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28345488/deep-infiltrating-endometriosis-and-endometrial-adenocarcinoma-express-high-levels-of-myostatin-and-its-receptors-messenger-rnas
#18
Patrizia Carrarelli, Lucia Funghi, Pasquapina Ciarmela, Gabriele Centini, Fernando M Reis, Cynthia Dela Cruz, Alberto Mattei, Silvia Vannuccini, Felice Petraglia
Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28342773/generation-of-enhanced-definitive-endoderm-from-human-embryonic-stem-cells-under-an-albumin-insulin-free-and-chemically-defined-condition
#19
Su Qu, Liang Yan, Bo Fang, Shoudong Ye, Ping Li, Shengyang Ge, Jian Wu, Di Qu, Houyan Song
AIM: To enhance survival and generation of definitive endoderm cells from human embryonic stem cells in a simple and reproducible system. MAIN METHODS: Definitive endoderm (DE) differentiation from human embryonic stem cells (hESCs) was induced under a chemical-defined condition withdrawn insulin supplement and serum albumin. We dissected influence of "alternative growth factors", WNT3A, BMP4 and bFGF in activin A-driven differentiation by detection of DE-associated genes expression and cell viability...
April 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28340932/predicting-first-trimester-pregnancy-outcome-derivation-of-a-multiple-marker-test
#20
Suneeta Senapati, Mary D Sammel, Samantha F Butts, Peter Takacs, Karine Chung, Kurt T Barnhart
OBJECTIVE: To predict first trimester pregnancy outcome using biomarkers in a multicenter cohort. DESIGN: Case-control study. SETTING: Three academic centers. PATIENT(S): Women with pain and bleeding in early pregnancy. INTERVENTION(S): Sera from women who were 5-12 weeks' gestational age with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage/spontaneous abortion (SAB) was analyzed by ELISA and immunoassay for activin A, inhibin A, P, A Disintegrin And Metalloprotease-12, pregnancy-associated plasma protein A (PAPP-A), pregnancy specific B1-glycoprotein (SP1), placental-like growth factor, vascular endothelial growth factor, glycodelin (Glyc), and hCG...
December 2016: Fertility and Sterility
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