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#35038317   2022/01/01 To Up

Activin A causes endothelial dysfunction of mouse aorta and human aortic cells.

Preeclampsia is a multisystem hypertensive disorder of pregnancy that remains one of the leading causes of maternal and perinatal morbidity and mortality worldwide. The widespread maternal endothelial dysfunction that underlies preeclampsia is thought to arise from excessive placental production of various factors combined with enhanced oxidative stress. While previous studies have reported elevated activin A in women diagnosed with preeclampsia, whether activin A can cause vascular dysfunction has not yet been thoroughly investigated. Here, we demonstrated that different subtypes of activin A receptors were localised to the endothelial and smooth muscle cells of mouse and human aortae. Then, the aorta of healthy female C57Bl6J mice (n=8) were incubated for 24 hours in various concentrations of recombinant activin A to mimic early pregnancy (5ng/mL), late pregnancy (20ng/mL) and preeclampsia (50ng/mL). Vascular reactivity as assessed by wire myography revealed that only the preeclamptic level of activin A impaired agonist-mediated endothelium-dependent relaxation by reducing the vasodilator prostanoid contribution to relaxation. However, agonist-mediated endothelium-independent mechanisms were unaffected. Further investigations carried out on human aortic endothelial cells suggested that the impairment of aorta relaxation could also be driven by increased endothelial cell permeability, and decreased cell viability, adherence and proliferation. This is the first direct evidence to show that activin A can induce endothelial dysfunction in whole blood vessels, suggesting that at high circulating levels it may contribute to the widespread endothelial dysfunction in women with preeclampsia.
Courtney Barber, Yann Yap, Natalie Josephine Hannan, Euan M Wallace, Sarah Arwen Marshall

1478 related Products with: Activin A causes endothelial dysfunction of mouse aorta and human aortic cells.

0.5 ml0.5 ml1.00 flask1.00 flask1.00 flask200 0.1ml (1mg/ml)200 200 1.00 flask200 1.00 flask

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#35034241   2022/01/16 To Up

An update on the ophthalmic features in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber syndrome is a rare autosomal dominant disease, characterised by systemic angiodysplasia. Dysfunction of the signalling pathway of β transforming growth factor is the main cause of HHT principally owing to mutations of the genes encoding for endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1). Clinical manifestations can range from mucocutaneous telangiectasia to organ arterio-venous malformations and recurrent epistaxis. The early clinical manifestations may sometimes be subtle, and diagnosis may be delayed. The main ophthalmic manifestations historically reported in HHT are haemorrhagic epiphora, and conjunctival telangiectasia present in 45-65% of cases, however, imaging with wide-field fluorescein angiography has recently shown peripheral retinal telangiectasia in 83% of patients. Optimal management of HHT requires both understanding of the clinical presentations and detection of early signs of disease. Advances in imaging methods in ophthalmology such as wide-field fluorescein angiography, spectral domain optical coherence tomography, and near infrared reflectance promise further insight into the ophthalmic signs of HHT towards improved diagnosis and early management of possible severe complications.
Solmaz Abdolrahimzadeh, Martina Formisano, Carla Marani, Siavash Rahimi

2336 related Products with: An update on the ophthalmic features in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).

100ug100 μg100ug Lyophilized100 μg100.00 ul

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#35024891   2022/01/13 To Up

Treatment with Soluble Activin Type IIB Receptor Ameliorates Ovariectomy-Induced Bone Loss and Fat Gain in Mice.

In postmenopausal osteoporosis, hormonal changes lead to increased bone turnover and metabolic alterations including increased fat mass and insulin resistance. Activin type IIB receptors bind several growth factors of the TGF-β superfamily and have been demonstrated to increase muscle and bone mass. We hypothesized that ActRIIB-Fc treatment could improve bone and muscle mass, inhibit fat accumulation, and restore metabolic alterations in an ovariectomy (OVX) model of postmenopausal osteoporosis.
Tero Puolakkainen, Petri Rummukainen, Vappu Pihala-Nieminen, Olli Ritvos, Eriika Savontaus, Riku Kiviranta

1213 related Products with: Treatment with Soluble Activin Type IIB Receptor Ameliorates Ovariectomy-Induced Bone Loss and Fat Gain in Mice.

100 μg96tests100 μg50ul100 μg96T96T100ug Lyophilized96T1 mL96 wells (1 kit)

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#35022746   2022/01/12 To Up

Human INHBB gene variant (c.1079T>C:p.Met360Thr) alters testis germ cell content, but does not impact fertility in mice.

Testicular derived inhibin B (α/βB dimers) acts in an endocrine manner to suppress pituitary production of follicle stimulating hormone (FSH), by blocking the actions of activins (βA/B/βA/B dimers). Previously, we identified a homozygous genetic variant (c.1079T>C:p.Met360Thr) arising from uniparental disomy of chromosome 2 in the INHBB gene (βB-subunit of inhibin B and activin B) in a man suffering from infertility (azoospermia). In this study, we aimed to test the causality of the p.Met360Thr variant in INHBB and testis function. Here, we used CRISPR/Cas9 technology to generate Inhbb  M364T/M364T mice, where mouse INHBB p.Met364 corresponds with human p.Met360. Surprisingly, we found that the testes of male Inhbb  M364T/M364T mutant mice were significantly larger compared with those of aged-matched wildtype littermates at 12 and 24 weeks of age. This was attributed to a significant increase in Sertoli cell and round spermatid number and, consequently, seminiferous tubule area, in Inhbb  M364T/M364T males compared to wildtype males. Despite this testis phenotype, male Inhbb  M364T/M364T mutant mice retained normal fertility. Serum hormone analyses however, indicated that the Inhbb  M364T variant resulted in reduced circulating levels of activin B, but did not affect FSH production. We also examined the effect of this p.Met360Thr, and an additional INHBB variant (c.314C>T: p.Thr105Met) found in another infertile man, on inhibin B and activin B in vitro biosynthesis. It was found that both INHBB variants resulted in a significant disruption to activin B in vitro biosynthesis. Together, this analysis supports that INHBB variants that limit activin B production have consequences for testis composition in males.
Brendan J Houston, Anne E O'Connor, Degang Wang, Georgia Goodchild, D Jo Merriner, Haitong Luan, Don F Conrad, Liina Nagirnaja, Kenneth I Aston, Sabine Kliesch, Margot J Wyrwoll, Corinna Friedrich, Frank Tüttelmann, Craig Harrison, Moira K O'Bryan, Kelly Walton

2061 related Products with: Human INHBB gene variant (c.1079T>C:p.Met360Thr) alters testis germ cell content, but does not impact fertility in mice.

1.00 flask100 μg1.00 flask1 mg1.00 flask10 ug100ug Lyophilized15ug100ug Lyophilized1.00 flask1mg

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#35013323   2022/01/10 To Up

The mA methyltransferase METTL3 regulates muscle maintenance and growth in mice.

Skeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for muscle homeostasis and the response to environmental insults. Yet, little is known about post-transcriptional mechanisms regulating such fluctuations while impacting muscle proteome. Here we report genome-wide analysis of mRNA methyladenosine (mA) dynamics of skeletal muscle hypertrophic growth following overload-induced stress. We show that increases in METTL3 (the mA enzyme), and concomitantly mA, control skeletal muscle size during hypertrophy; exogenous delivery of METTL3 induces skeletal muscle growth, even without external triggers. We also show that METTL3 represses activin type 2 A receptors (ACVR2A) synthesis, blunting activation of anti-hypertrophic signaling. Notably, myofiber-specific conditional genetic deletion of METTL3 caused spontaneous muscle wasting over time and abrogated overload-induced hypertrophy; a phenotype reverted by co-administration of a myostatin inhibitor. These studies identify a previously unrecognized post-transcriptional mechanism promoting the hypertrophic response of skeletal muscle via control of myostatin signaling.
Jennifer M Petrosino, Scott A Hinger, Volha A Golubeva, Juan M Barajas, Lisa E Dorn, Chitra C Iyer, Hui-Lung Sun, W David Arnold, Chuan He, Federica Accornero

1963 related Products with: The mA methyltransferase METTL3 regulates muscle maintenance and growth in mice.

1 Set48 assays 1 Set 25 MG100 μgProtein1 Set1mg1 Set

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#35008873   2021/12/31 To Up

TGF-β Potentiates the Cytotoxicity of Cadmium by Induction of a Metal Transporter, ZIP8, Mediated by the ALK5-Smad2/3 and ALK5-Smad3-p38 MAPK Signal Pathways in Cultured Vascular Endothelial Cells.

Vascular endothelial cells cover the luminal surface of blood vessels in a monolayer and play a role in the regulation of vascular functions, such as the blood coagulation-fibrinolytic system. When the monolayer is severely or repeatedly injured, platelets aggregate at the damaged site and release transforming growth factor (TGF)-β in large quantities from their α-granules. Cadmium is a heavy metal that is toxic to various organs, including the kidneys, bones, liver, and blood vessels. Our previous study showed that the expression level of Zrt/Irt-related protein 8 (ZIP8), a metal transporter that transports cadmium from the extracellular fluid into the cytosol, is a crucial factor in determining the sensitivity of vascular endothelial cells to cadmium cytotoxicity. In the present study, TGF-β was discovered to potentiate cadmium-induced cytotoxicity by increasing the intracellular accumulation of cadmium in cells. Additionally, TGF-β induced the expression of ZIP8 via the activin receptor-like kinase 5-Smad2/3 signaling pathways; Smad3-mediated induction of ZIP8 was associated with or without p38 mitogen-activated protein kinase (MAPK). These results suggest that the cytotoxicity of cadmium to vascular endothelial cells increases when damaged endothelial monolayers that are highly exposed to TGF-β are repaired.
Keisuke Ito, Tomoya Fujie, Masahiro Shimomura, Tsuyoshi Nakano, Chika Yamamoto, Toshiyuki Kaji

1866 related Products with: TGF-β Potentiates the Cytotoxicity of Cadmium by Induction of a Metal Transporter, ZIP8, Mediated by the ALK5-Smad2/3 and ALK5-Smad3-p38 MAPK Signal Pathways in Cultured Vascular Endothelial Cells.

1.00 flask1 Set1.00 flask12 Pieces/Box

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#35005539   2021/12/09 To Up

Structures of activin ligand traps using natural sets of type I and type II TGFβ receptors.

The 30+ unique ligands of the TGFβ family signal by forming complexes using different combinations of type I and type II receptors. Therapeutically, the extracellular domain of a single receptor fused to an Fc molecule can effectively neutralize subsets of ligands. Increased ligand specificity can be accomplished by using the extracellular domains of both the type I and type II receptor to mimic the naturally occurring signaling complex. Here, we report the structure of one "type II-type I-Fc" fusion, ActRIIB-Alk4-Fc, in complex with two TGFβ family ligands, ActA, and GDF11, providing a snapshot of this therapeutic platform. The study reveals that extensive contacts are formed by both receptors, replicating the ternary signaling complex, despite the inherent low affinity of Alk4. Our study shows that low-affinity type I interactions support altered ligand specificity and can be visualized at the molecular level using this platform.
Erich J Goebel, Chandramohan Kattamuri, Gregory R Gipson, Lavanya Krishnan, Moises Chavez, Magdalena Czepnik, Michelle C Maguire, Rosa Grenha, Maria HÃ¥kansson, Derek T Logan, Asya V Grinberg, Dianne Sako, Roselyne Castonguay, Ravindra Kumar, Thomas B Thompson

1838 related Products with: Structures of activin ligand traps using natural sets of type I and type II TGFβ receptors.

100 TESTS10 mg lyophilized1 ml

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#35003118   2021/12/22 To Up

Activin and BMP Signaling Activity Affects Different Aspects of Host Anti-Nematode Immunity in .

The multifaceted functions ranging from cellular and developmental mechanisms to inflammation and immunity have rendered TGF-ß signaling pathways as critical regulators of conserved biological processes. Recent studies have indicated that this evolutionary conserved signaling pathway among metazoans contributes to the anti-nematode immune response. However, functional characterization of the interaction between TGF-ß signaling activity and the mechanisms activated by the immune response against parasitic nematode infection remains unexplored. Also, it is essential to evaluate the precise effect of entomopathogenic nematode parasites on the host immune system by separating them from their mutualistic bacteria. Here, we investigated the participation of the TGF-ß signaling branches, activin and bone morphogenetic protein (BMP), to host immune function against axenic or symbiotic nematodes (parasites lacking or containing their mutualistic bacteria, respectively). Using larvae carrying mutations in the genes coding for the TGF-ß extracellular ligands Daw and Dpp, we analyzed the changes in survival ability, cellular immune response, and phenoloxidase (PO) activity during nematode infection. We show that infection with axenic decreases the mortality rate of mutants, but not mutants. Following axenic or symbiotic . infection, both and mutants contain only plasmatocytes. We further detect higher levels of gene expression in mutants upon infection with axenic nematodes and and gene expression in mutants upon infection with symbiotic nematodes compared to controls. Finally, following symbiotic infection, mutants have higher PO activity relative to controls. Together, our findings reveal that while Dpp/BMP signaling activity modulates the DUOX/ROS response to axenic infection, Daw/activin signaling activity modulates the antimicrobial peptide and melanization responses to axenic infection. Results from this study expand our current understanding of the molecular and mechanistic interplay between nematode parasites and the host immune system, and the involvement of TGF-ß signaling branches in this process. Such findings will provide valuable insight on the evolution of the immune role of TGF-ß signaling, which could lead to the development of novel strategies for the effective management of human parasitic nematodes.
Yaprak Ozakman, Dhaivat Raval, Ioannis Eleftherianos

1135 related Products with: Activin and BMP Signaling Activity Affects Different Aspects of Host Anti-Nematode Immunity in .

0.1ml (1mg/ml)0.1ml100 μg0.1ml100 ul100 ul100 μg0.1ml0.1ml100 ul100 ul100 ul

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#34995570   2022/01/04 To Up

Snake Technique in Osler's Disease-associated Thoracoabdominal Aortic Aneurysm.

Osler's disease is an autosomal dominant disorder characterized by epistaxis, telangiectases, and arteriovenous malformations of the internal organs. We, herein, report the first published case of dissecting thoracoabdominal aortic aneurysm repair in a 66 year-old woman with hereditary hemorrhagic telangiectasia associated with activin receptor-like kinase 1 gene mutations. We maintained the activated clotting time around 400 seconds during cardiopulmonary bypass to avoid lethal hemorrhage from telangiectases or arteriovenous malformations. The Adamkiewicz artery could not be identified on imaging studies preoperatively. We, therefore, used the 'Snake technique' for intercostal revascularization, which was effective in preventing paraplegia.
Saki Bessho, Hisato Ito, Bun Nakamura, Yu Shomura, Yoshito Ogihara, Norikazu Yamada, Motoshi Takao

1374 related Products with: Snake Technique in Osler's Disease-associated Thoracoabdominal Aortic Aneurysm.

96 tests96 tests96 tests

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