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Activin A

Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
March 12, 2018: Biochimie
Ifigeneia Kalampouka, Angel van Bekhoven, Bradley T Elliott
Ageing is associated with a general reduction of physiological function and a reduction of muscle mass and strength. Endocrine factors such as myostatin, activin A, growth and differentiation factor 11 (GDF-11) and their inhibitory peptides influence muscle mass in health and disease. We hypothesised that myocytes cultured in plasma from older and younger individuals would show an ageing effect, with reduced proliferation and differentiation in older environments. C2C12 myoblasts were grown as standard and stimulated with media conditioned with 5% plasma from healthy male participants that were either younger ( n = 6, 18-35 years of age) or older ( n = 6, >57 years of age)...
2018: Frontiers in Physiology
Tetsuya Ikemoto, Rui Feng, Mitsuo Shimada, Yu Saito, Shuichi Iwahashi, Yuji Morine, Satoru Imura
OBJECTIVES: We aimed to develop a simple protocol for deriving insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ADSCs). We established a 2-step creation method and an acceleration strategy with a histone deacetylase inhibitor that promoted a pro-endocrine pancreatic lineage. METHODS: We seeded ADSCs in 96-well dishes and cultured in Dulbecco's modified Eagle's medium/F12 medium containing 1% fetal bovine serum, 1% B27 supplement, 1% N2 supplement, 50-ng/mL human activin A, and 10-nM exendin-4 for step 1 of differentiation (7 days)...
April 2018: Pancreas
Chien-Huang Lin, Chung-Huang Shih, Yu-Chang Lin, You-Lan Yang, Bing-Chang Chen
BACKGROUND: In idiopathic pulmonary fibrosis, the interaction of CXCL12 and CXC receptor 4 (CXCR4) plays a critical role in lung fibrosis. Connective tissue growth factor (CTGF) overexpression underlies the development of pulmonary fibrosis. Our previous report showed that the Rac1-dependent extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and activator protein (AP)-1 pathways are involved in CXCL12-generated CTGF expression in human lung fibroblasts (WI-38)...
March 2, 2018: Journal of Biomedical Science
L Martin, N Zouhiri, M Audran, A Marchand
New therapeutic proteins that trap circulating members of the TGF beta superfamily (activins and growth differentiation factors) show promising effects on erythropoiesis and muscular growth. They are dimeric recombinant fusion proteins composed of the extracellular domain of a human activin receptor (ActRIIA or IIB) linked to the Fc part of human IgG1. Sotatercept (ActRIIA-Fc) and Luspatercept (a modified ActRIIB-Fc) in particular are now in phase 2/3 of clinical trials against anemia and included in the prohibited list established by the World Anti-Doping Agency...
March 2, 2018: Drug Testing and Analysis
Andreas Lodberg, Marco Eijken, Bram C J van der Eerden, Mette Wendelboe Okkels, Jesper Skovhus Thomsen, Annemarie Brüel
Disuse causes a rapid and substantial bone loss distinct in its pathophysiology from the bone loss associated with cancers, age, and menopause. While inhibitors of the activin-receptor signaling pathway (IASPs) have been shown to prevent ovariectomy- and cancer-induced bone loss, their application in a model of disuse osteopenia remains to be tested. Here, we show that a soluble activin type IIA receptor (ActRIIA-mFc) increases diaphyseal bone strength and cancellous bone mass, and mitigates the loss of femoral neck bone strength in the Botulinum Toxin A (BTX)-model of disuse osteopenia in female C57BL/6J mice...
February 27, 2018: Bone
Mirza Muhammad Fahd Qadir, Silvia Álvarez-Cubela, Dagmar Klein, Giacomo Lanzoni, Carlos García-Santana, Abelardo Montalvo, Fabiola Pláceres-Uray, Emilia Maria Cristina Mazza, Camillo Ricordi, Luca Alessandro Inverardi, Ricardo Luis Pastori, Juan Domínguez-Bendala
Treatment of human pancreatic non-endocrine tissue with Bone Morphogenetic Protein 7 (BMP-7) leads to the formation of glucose-responsive β-like cells. Here, we show that BMP-7 acts on extrainsular cells expressing PDX1 and the BMP receptor activin-like kinase 3 (ALK3/BMPR1A). In vitro lineage tracing indicates that ALK3+ cell populations are multipotent. PDX1+ /ALK3+ cells are absent from islets but prominently represented in the major pancreatic ducts and pancreatic duct glands. We identified the purinergic receptor P2Y1 (P2RY1) as a surrogate surface marker for PDX1...
February 27, 2018: Cell Reports
Shengjie Tian, Jianhua Zhu, Yaogang Lu
BACKGROUND: Fibrodysplasia ossificans progressiva (FOP), an ultra-rare and disabling genetic disorder of skeletal malformations and progressive heterotopic ossification, is caused by heterozygous activating mutations in activin A receptor, type I/activin-like kinase 2 (ACVR1/ALK2). The rarity of the disease makes it common to make a misdiagnosis and cause mismanagement. CASE PRESENTATION: We reported a case of a sixteen-year-old male patient who had suffered from pain and swelling in the biopsy site for two months...
February 27, 2018: BMC Medical Genetics
Li Li, Min Tong, Yi-Ting Zhao, Yun He, Hong-Yu Zhou, Guo-Fu Zhang, Yuan-Jin Zhang
Using bone biopsy samples, we examined whether osteolytic cytokine profile is changed in situ in bone samples of metastatic multiple myeloma, and whether this creates an environment of lysis within the bone to which it has spread. This also produces the clinical features of increased circulating plasma calcium, and deleterious effects on the kidney.Using multiple myeloma biopsy and cell extracts from bone metastatic lesions, Bruton kinase, a tyrosine kinase, was demonstrated to be translocated to the membrane...
January 2018: Medicine (Baltimore)
Martina Belli, Nahoko Iwata, Tomoko Nakamura, Akira Iwase, Dwayne Stupack, Shunichi Shimasaki
Germline knockout studies in female mice demonstrated an essential role for FOXL2 in early follicle development, while an inducible granulosa cell (GC) specific deletion of Foxl2 in adults has shown ovary-to-testis somatic sex reprogramming. In women, over 120 different germline mutations in the FOXL2 gene have been shown to cause blepharophimosis/ptosis/epicantus inversus syndrome associated with or without primary ovarian insufficiency. By contrast, a single somatic mutation (FOXL2C134W) accounts for almost all adult-type GC tumors (aGCTs)...
February 19, 2018: Endocrinology
A I Gonçalves, M Rotherham, H Markides, M T Rodrigues, R L Reis, M E Gomes, A J El Haj
Stem cell therapies hold potential to stimulate tendon regeneration and homeostasis, which is maintained in response to the native mechanical environment. Activins are members of the mechano-responsive TGF-β superfamily that participates in the regulation of several downstream biological processes. Mechanosensitive membrane receptors such as activin can be activated in different types of stem cells via magnetic nanoparticles (MNPs) through remote magnetic actuation resulting in cell differentiation. In this work, we target the Activin receptor type IIA (ActRIIA) in human adipose stem cells (hASCs), using anti-ActRIIA functionalized MNPs, externally activated through a oscillating magnetic bioreactor...
February 19, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Hong-Jie Lu, Jing Yan, Pei-Ying Jin, Gui-Hong Zheng, Hai-Lin Zhang, Ming Bai, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
OBJECTIVE: The aim of this study was to evaluate the mechanisms involved with miRNA-708 and its targeting of bone morphogenetic protein and activin membrane-bound inhibitor in cell proliferation, migration, and apoptosis in mice with melanoma via the Wnt and transforming growth factor β signaling pathways. METHODS: Sixty mice were recruited of which 40 were subsequently assigned into the experimental group (22 mice were successfully established as melanoma model and 18 mice used in tumor xenograft), and the normal control group consisted of 20 mice...
January 1, 2018: Technology in Cancer Research & Treatment
Eric Haertel, Natasha Joshi, Paul Hiebert, Manfred Kopf, Sabine Werner
Healing of skin wounds is orchestrated by various types of immune cells, but little is known about the role of FoxP3+ regulatory T cells (Tregs) in this process. Here we determined if Tregs are important for wound healing in normal mice and if they contribute to the accelerated healing of mice overexpressing the growth and differentiation factor activin. Diphtheria-toxin induced Treg depletion prior to injury caused impaired healing characterized by delayed re-epithelialization, reduced wound contraction and impaired vessel maturation...
February 19, 2018: European Journal of Immunology
Jui M Dave, Teodelinda Mirabella, Scott D Weatherbee, Daniel M Greif
The murine embryonic blood-brain barrier (BBB) consists of endothelial cells (ECs), pericytes (PCs), and basement membrane. Although PCs are critical for inducing vascular stability, signaling pathways in PCs that regulate EC morphogenesis during BBB development remain unexplored. Herein, we find that murine embryos lacking the transforming growth factor β (TGF-β) receptor activin receptor-like kinase 5 (Alk5) in brain PCs (mutants) develop gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH)...
February 8, 2018: Developmental Cell
Elisenda Alsina-Sanchís, Yaiza García-Ibáñez, Ana M Figueiredo, Carla Riera-Domingo, Agnès Figueras, Xavier Matias-Guiu, Oriol Casanovas, Luisa M Botella, Miquel A Pujana, Antoni Riera-Mestre, Mariona Graupera, Francesc Viñals
OBJECTIVE: ALK1 (activin-receptor like kinase 1) is an endothelial cell-restricted receptor with high affinity for BMP (bone morphogenetic protein) 9 TGF-β (transforming growth factor-β) family member. Loss-of-function mutations in ALK1 cause a subtype of hereditary hemorrhagic telangiectasia-a rare disease characterized by vasculature malformations. Therapeutic strategies are aimed at reducing potential complications because of vascular malformations, but currently, there is no curative treatment for hereditary hemorrhagic telangiectasia...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Irshad Ahmad, Dhanashree D Jagtap, C Selvaa Kumar, Nafisa H Balasinor, A M Babitha Rani, Deepak Agarwal, Neelam Saharan
The inhibins are disulphide-linked heterodimeric glycoproteins that belong to the TGFβ superfamily. Inhibins have been well studied in mammals but the information about their structure and function is very limited in lower vertebrates. The aim of the present study was to characterize inhibin-A and to understand its receptor binding interaction, and to evaluate its biological function in Clarias batrachus. Structure prediction of inhibin-A revealed two glycosylation sites on inhibin-α (Asp262 and Asn334). Docking of inhibin-A with its receptor; betaglycan and Act RIIA showed that residues Ser321, Gly324 and Leu325 of inhibin-α are involved in high affinity binding with betaglycan while inhibin-βA bound to Act RIIA by forming hydrogen bonds...
February 10, 2018: General and Comparative Endocrinology
Yuanyi Zhang, Yan Qi, Yang Zhao, Hongyan Sun, Jingyan Ge, Zhonghui Liu
Activin A is a pleiotropic cytokine belonging to the transforming growth factor β superfamily. Abnormal expression of activin A is associated with tumorigenesis. Multiple myeloma is characterized by the development of osteolytic disease, which ultimately leads to cachexia. However, the involvement of activin A in myeloma cell viability and apoptosis remains to be fully elucidated. For this purpose, mouse myeloma NS-1 cells were treated with activin A, and subsequently subjected to 5-bromo-2'-deoxyuridine analysis, Hoechst 33342 staining, flow cytometry and western blot analysis...
February 2018: Oncology Letters
Concha Nieto, Rafael Bragado, Cristina Municio, Elena Sierra-Filardi, Bárbara Alonso, María M Escribese, Jorge Domínguez-Andrés, Carlos Ardavín, Antonio Castrillo, Miguel A Vega, Amaya Puig-Kröger, Angel L Corbí
GM-CSF promotes the functional maturation of lung alveolar macrophages (A-MØ), whose differentiation is dependent on the peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor. In fact, blockade of GM-CSF-initiated signaling or deletion of the PPARγ-encoding gene PPARG leads to functionally defective A-MØ and the onset of pulmonary alveolar proteinosis. In vitro , macrophages generated in the presence of GM-CSF display potent proinflammatory, immunogenic and tumor growth-limiting activities...
2018: Frontiers in Immunology
Jingxi Ma, Lina Zhang, Tengfei Niu, Chibo Ai, Gongwei Jia, Xinhao Jin, Lan Wen, Keming Zhang, Qinbin Zhang, Changqing Li
The recent suggestion that growth differentiation factor 11 (GDF11) acts as a rejuvenation factor has remained controversial. However, in addition to its role in aging, the relationship between GDF11 and cerebral ischemia is still an important area that needs more investigation. Here we examined effects of GDF11 on angiogenesis and recovery of neurological function in a rat model of stroke. Exogenous recombinant GDF11 (rGDF11) at different doses were directly injected into the tail vein in rats subjected to cerebral ischemia/reperfusion (I/R)...
February 9, 2018: Brain Research Bulletin
Juli E Jones, Samuel M Cadena, Chenguang Gong, Xiaomei Wang, Zhiping Chen, Sharon X Wang, Chad Vickers, Hong Chen, Estelle Lach-Trifilieff, John R Hadcock, David J Glass
The age-related effects of GDF11 have been a subject of controversy. Here, we find that elevated GDF11 causes signs of cachexia in mice: reduced food intake, body weight, and muscle mass. GDF11 also elicited a significant elevation in plasma Activin A, previously shown to contribute to the loss of skeletal muscle. The effects of GDF11 on skeletal muscle could be reversed by administration of antibodies to the Activin type II receptors. In addition to the effects on muscle, GDF11 increased plasma GDF15, an anorectic agent...
February 6, 2018: Cell Reports
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