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Activin A AND Beta cells

Niina K Palin, Johanna Savikko, Arja Pasternack, Jukka M Rintala, Bhanu Kalra, Shivani Mistry, Ajay Kumar, Marie-Paule Roth, Heikki Helin, Olli Ritvos
BACKGROUND: Activins are members of the TGF-beta superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation. METHODS: The study was done in kidney transplantation and renal ischemia-reperfusion models in the rat. Soluble activin type 2 receptor (sActRIIB-Fc) was used to inhibit activin signaling...
October 12, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Po-Shuen Lin, Hsiao-Hua Chang, Chien-Yang Yeh, Mei-Chi Chang, Chiu-Po Chan, Han-Yueh Kuo, Hsin-Cheng Liu, Wan-Chuen Liao, Po-Yuan Jeng, Sin-Yuet Yeung, Jiiang-Huei Jeng
BACKGROUND/PURPOSE: In order to clarify the role of transforming growth factor beta 1 (TGF-β1) in pulp repair/regeneration responses, we investigated the differential signaling pathways responsible for the effects of TGF-β1 on collagen turnover, matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human dental pulp cells. METHODS: Pulp cells were exposed to TGF-β1 with/without pretreatment and coincubation by 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenyl mercapto)butadiene (U0126; a mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] inhibitor) and 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H- imidazol-2-yl)-benzamide hydrate (SB431542; an activin receptor-like kinase-5/Smad signaling inhibitor)...
October 6, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Yi-Fei Qi, Long Wu, Zi-Qian Li, Meng-Ling Wu, Hai-Fang Wang, Ka-Ying Chan, Lin-Lin Lu, Shao-Hui Cai, Hong-Sheng Wang, Jun Du
Nodal is a member of transforming growth factor beta (TGF-β) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the β-catenin nuclear translocation...
October 15, 2016: Archives of Biochemistry and Biophysics
Amaya García de Vinuesa, Matteo Bocci, Kristian Pietras, Peter Ten Dijke
Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs)...
August 15, 2016: Biochemical Society Transactions
Manne Mudhu Sunitha, Lokanathan Srikanth, Pasupuleti Santhosh Kumar, Chodimella Chandrasekhar, Potukuchi Venkata Gurunadha Krishna Sarma
Haematopoietic stem cells (HSCs) possess multipotent ability to differentiate into various types of cells on providing appropriate niche. In the present study, the differentiating potential of human HSCs into β-cells of islets of langerhans was explored. Human HSCs were apheretically isolated from a donor and cultured. Phenotypic characterization of CD34 glycoprotein in the growing monolayer HSCs was confirmed by immunocytochemistry and flow cytometry techniques. HSCs were induced by selection with beta cell differentiating medium (BDM), which consists of epidermal growth factor (EGF), fibroblast growth factor (FGF), transferrin, Triiodo-l-Tyronine, nicotinamide and activin A...
October 2016: Cell Biology International
Saki Yokokura, Nobuhiro Kanaji, Akira Tadokoro, Shigeyuki Yokokura, Norimitsu Kadowaki, Shuji Bandoh
PURPOSE OF THE STUDY: Confluence-dependent resistance (CDR) is a phenomenon in which the efficacy of anti-cancer agents decreases when cell density increases. CDR in lung cancer has never been reported. The purpose of this study is to investigate if CDR can occur in NSCLC cells and to find a role for transforming growth factor (TGF)-β as a mechanism of CDR. MATERIALS AND METHODS: Non-small cell lung cancer (NSCLC) cell lines A549 and H2228 were exposed to cisplatin in a variety of cell density conditions...
May 2016: Experimental Lung Research
Zheng Min, Ma Junwu
Gout is one of the most common inflammatory arthritis caused by hyperuricaemia, which is affected by both genetic factors and environmental factors. Early researches show that a few of rare monogenic mutations, such as PRPS1 and HPRT1 mutations, lead to abnormal purine anabolism and then cause hyperuricaemia and gout. In recent years, genome-wide association studies (GWAS) have identified dozens of susceptibility loci and/or candidate genes associated with hyperuricemia and gout. Loss-of-function mutations in SLC2A9, SLC22A11, and SLC22A12 cause hereditary hypouricaemia, while their overexpression may increase the reabsorption of uric acid...
April 2016: Yi Chuan, Hereditas
R Wijayarathna, D M de Kretser
BACKGROUND: Activins are members of the pleiotrophic family of the transforming growth factor-beta (TGF-β) superfamily of cytokines, initially isolated for their capacity to induce the release of FSH from pituitary extracts. Subsequent research has demonstrated that activins are involved in multiple biological functions including the control of inflammation, fibrosis, developmental biology and tumourigenesis. This review summarizes the current knowledge on the roles of activin in reproductive and developmental biology...
April 2016: Human Reproduction Update
Eunate Gallardo-Vara, Francisco J Blanco, Mercè Roqué, Scott L Friedman, Toru Suzuki, Luisa M Botella, Carmelo Bernabeu
After endothelial injury, the transcription factor Krüppel-like factor 6 (KLF6) translocates into the cell nucleus to regulate a variety of target genes involved in angiogenesis, vascular repair and remodeling, including components of the membrane transforming growth factor beta (TGF-β) receptor complex such as endoglin and activin receptor-like kinase 1. The membrane metalloproteinase 14 (MMP14 or MT1-MMP) targets endoglin to release soluble endoglin and is involved in vascular inflammation and endothelial tubulogenesis...
April 2016: Angiogenesis
Hendrik Ungefroren, Ayman Hyder, Maren Schulze, Karim M Fawzy El-Sayed, Evelin Grage-Griebenow, Andreas K Nussler, Fred Fändrich
Adult stem or programmable cells hold great promise in diseases in which damaged or nonfunctional cells need to be replaced. We have recently demonstrated that peripheral blood monocytes can be differentiated in vitro into cells resembling specialized cell types like hepatocytes and pancreatic beta cells. During phenotypic conversion, the monocytes downregulate monocyte/macrophage differentiation markers, being indicative of partial dedifferentiation, and are partially reprogrammed to acquire a state of plasticity along with expression of various markers of pluripotency and resumption of mitosis...
2016: Stem Cells International
Su-Ren Chen, Yi-Xun Liu
Testis cords, embryonic precursors of the seminiferous tubules, are fundamental for testis structure and function. Delay or disruption of testis cord formation could result in gonadal dysgenesis. Although mechanisms regulating testis cord formation during sex determination have been well-studied, the genes and signaling pathways involving in testis cord maintenance after the cords have formed are not well characterized. It is now clear that the maintenance of cord structure is an active process. In this review, we summarize the recent findings regarding the regulation of testis cord integrity by a series of Sertoli cell transcription factors, including the WT1-SOX8/SOX9-beta-CATENIN-DHH network, GPR56, STIM1, and NR0B1 (also known as DAX1)...
February 2016: Biology of Reproduction
Anne R O'Connell, Kenneth P McNatty, Peter R Hurst, Thomas E Spencer, Fuller W Bazer, Karen L Reader, Peter D Johnstone, George H Davis, Jennifer L Juengel
The activin pathway has been postulated to be involved in regulation of multiple reproductive processes important for survival of the conceptus. These processes include luteinisation of the follicular cells and thus function of the corpus luteum, early embryo development and uterine function including implantation of the conceptus. Therefore, the aim of the current study was to determine whether the concentrations of activin A and follistatin (FST), an activin-binding protein, differed between ewes with a lifetime history of enhanced or reduced embryonic survival (ES)...
March 2016: Journal of Endocrinology
Larissa Eiselein, Tun Nyunt, Michael W Lamé, Kit F Ng, Dennis W Wilson, John C Rutledge, Hnin H Aung
Studies have suggested a link between the transforming growth factor beta 1 (TGF-β1) signaling cascade and the stress-inducible activating transcription factor 3 (ATF3). We have demonstrated that triglyceride-rich lipoproteins (TGRL) lipolysis products activate MAP kinase stress associated JNK/c-Jun pathways resulting in up-regulation of ATF3, pro-inflammatory genes and induction of apoptosis in human aortic endothelial cells. Here we demonstrate increased release of active TGF-β at 15 min, phosphorylation of Smad2 and translocation of co-Smad4 from cytosol to nucleus after a 1...
2015: PloS One
Lauren Drowley, Chad Koonce, Samantha Peel, Anna Jonebring, Alleyn T Plowright, Steven J Kattman, Henrik Andersson, Blake Anson, Bradley J Swanson, Qing-Dong Wang, Gabriella Brolen
Several progenitor cell populations have been reported to exist in hearts that play a role in cardiac turnover and/or repair. Despite the presence of cardiac stem and progenitor cells within the myocardium, functional repair of the heart after injury is inadequate. Identification of the signaling pathways involved in the expansion and differentiation of cardiac progenitor cells (CPCs) will broaden insight into the fundamental mechanisms playing a role in cardiac homeostasis and disease and might provide strategies for in vivo regenerative therapies...
February 2016: Stem Cells Translational Medicine
Kyosuke Hino, Makoto Ikeya, Kazuhiko Horigome, Yoshihisa Matsumoto, Hayao Ebise, Megumi Nishio, Kazuya Sekiguchi, Mitsuaki Shibata, Sanae Nagata, Shuichi Matsuda, Junya Toguchida
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by extraskeletal bone formation through endochondral ossification. FOP patients harbor point mutations in ACVR1 (also known as ALK2), a type I receptor for bone morphogenetic protein (BMP). Two mechanisms of mutated ACVR1 (FOP-ACVR1) have been proposed: ligand-independent constitutive activity and ligand-dependent hyperactivity in BMP signaling. Here, by using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs), we report a third mechanism, where FOP-ACVR1 abnormally transduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling but not BMP signaling...
December 15, 2015: Proceedings of the National Academy of Sciences of the United States of America
Mi-Nyeu Kim, Young Il Kim, Chunghee Cho, Kelly E Mayo, Byung-Nam Cho
Originally, activins were identified as stimulators of FSH release in reproduction. Other activities, including secondary axis formation in development, have since been revealed. Here, we investigated the influence of activin βA on the body, including the gastro-intestinal (GI) tract. Initially, the activin βA protein was detected in the serum proportional to the amount of pCMV-rAct plasmid injected. The induced level of activin βA in muscle was higher in female than male mice. Subsequent results revealed that stomach and intestine were severely damaged in pCMV-rAct-injected mice...
December 2015: Molecules and Cells
Lixin Lin, Yuting Wang, Wenyi Liu, Yong Huang
Keloids are scars characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Hypernomic growth of fibroblast cells and excessive accumulation of collagens, especially collagen I, made important contribution to keloid formation. Transforming growth factor-beta 1 (TGF-β1) was a key ruler for the dermal fibrosis. Here, we found that BMP and activin membrane-bound inhibitor (BAMBI), a pseudo-receptor of TGF-β1, was being decreased during the human keloid development and in vitro keloid cell growth...
2015: International Journal of Clinical and Experimental Medicine
J A Maring, L A van Meeteren, M J Goumans, Peter Ten Dijke
Transforming growth factor-β (TGF-β) is a multifunctional cytokine with important roles in embryogenesis and maintaining tissue homeostasis during adult life. There are three isoforms of TGF-β, i.e., TGF-β1, -β2, and -β3, which signal by binding to a complex of transmembrane type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. In most cell types TGF-β signals via TGF-β type II receptor (TβRII) and TβRI, also termed activin receptor-like kinase 5 (ALK5)...
2016: Methods in Molecular Biology
Wenlin Li, Wanguo Wei, Sheng Ding
The transforming growth factor-β (TGF-β) family of cytokines, including TGF-β, bone morphogenic proteins (BMPs), and activin/nodal, is a group of crucial morphogens in embryonic development, and plays key roles in modulating stem/progenitor cell fate. TGF-β signaling is essential in maintaining the pluripotency of human pluripotent stem cells (hPSCs), including both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), and its modulation can direct lineage-specific differentiation...
2016: Methods in Molecular Biology
Ning Qin, Xian-Cong Fan, Xiao-Xing Xu, Thobela Louis Tyasi, Shi-Jun Li, Ying-Ying Zhang, Man-Li Wei, Ri-Fu Xu
Forkhead box L2 (FOXL2) is a member of the forkhead nuclear factor 3 gene family and plays an essential role in ovarian growth and maturation in mammals. However, its potential effects and regulative mechanism in development of chicken ovarian prehierarchical follicles remain unexplored. In this study, the cooperative effects of FOXL2 with activin A, growth differentiation factor-9 (GDF9) and follistatin, three members of the transforming growth factor beta (TGF-β) superfamily that were previously suggested to exert a critical role in follicle development was investigated...
2015: PloS One
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