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Intracrine signalling of activin A in hepatocytes upregulates connective tissue growth factor (CTGF/CCN2) expression.

BACKGROUND/AIMS: Up to now, the effect of activin A on the expression of the important transforming growth factor (TGF)-beta downstream modulator connective tissue growth factor (CTGF) is not known, but might be of relevance for the functional effects of this cytokine on several liver cell types. METHODS: In this study, activin A-dependent CTGF expression in hepatocytes (PC) primed by exogenous activin A and in PC maintained under complete activin-free culture conditions was analysed by Western blots, metabolic labelling, gene silencing, reverse transcriptase-polymerase chain reaction (RT-PCR

A study of luteal phase expression of inhibin, activin, and follistatin subunits in the endometrium of women with recurrent miscarriage.

OBJECTIVE: To compare the luteal phase endometrial expression of inhibin, activin, and follistatin subunits in women with recurrent miscarriage compared to a control group. Other parameters of luteal function assessed included Doppler blood flow, serum biochemical markers, and histopathology. DESIGN: This was a prospective case control study. SETTING: The study was conducted in a tertiary care hospital of Sheffield, United Kingdom. PATIENT(S): Thirty-three women with recurrent miscarriage and 10 women with no previous history of miscarriage (control group) were recruited. INTERVENTION(S):

Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.

Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia. So far, two loci have been demonstrated for ORW. Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently identified as the ORW1 gene. A second locus, designated ORW2, was mapped to chromosome 12. Here we report a new 4 cM interval for ORW2 that does not overlap with any previously defined. A 1.38-Mb YAC contig spans the entire interval. It includes the activin receptor like kinase 1 gene (ACVRLK1 or ALK1), a member of the serine-threonine kinas

Expression of alpha, beta A and beta B subunits of inhibin or activin and follistatin in rat pancreatic islets.

We first detected the mRNA expression of follistatin and three subunits of inhibin/activin in rat pancreatic islets by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry using anti-follistatin serum (against residues 123-134) revealed that follistatin was localized only in insulin-producing B cells. Although the beta A subunit was detectable in the islets, the immunostainable cell types were completely different with two beta A antisera, i.e. anti-beta A (1-10)-Tyr stained B cells, while anti-beta A (87-99) stained glucagon-producing A cells. This inconsistent immun

A surface component on GH3 pituitary cells that recognizes transforming growth factor-beta, activin, and inhibin.

We have examined the ability of various forms of activin and inhibin, which are structurally related to transforming growth factor-beta (TGF-beta), to interact with various types of cell surface TGF-beta binding sites. Activin AB, inhibin A, and inhibin B were unable to compete with 125I-TGF-beta 1 for binding to the TGF-beta receptor types I, II, or III that coexist in human skin fibroblasts, rat liver epithelial cells, and mink lung epithelial cells. In contrast, activins and inhibins effectively competed for TGF-beta 1 binding to GH3 rat pituitary tumor cells. Binding of TGF-beta 1 to GH3 c…

Activin pathway inhibition and rapid progression of malignancy in pulmonary arterial hypertension: A case series and hypothesis.

The increased risk of malignancy in PAH and the immunologic duality of activin raise important questions about the long-term implications of activin signal inhibitors, particularly in patients with preexisting or latent malignancies. Emerging real-world observations raise questions regarding potential associations between sotatercept exposure and malignancy development or progression. We describe a series of malignancies that occurred in patients treated with sotatercept. While these cases do not establish causality, they highlight the need for vigilance and further study.

Elevated Activin-A serum levels in patients with acute peripartum cardiomyopathy and during left ventricular recovery.

BACKGROUND AND AIMS: Peripartum cardiomyopathy (PPCM) is an idiopathic form of heart failure occurring in the peripartum phase. Elevated circulating levels of the senescence-associated-secretory-phenotype (SASP) factor Activin-A have been associated with heart failure severity in acute PPCM patients at baseline diagnosis. Here, we investigated Activin-A serum levels in the German PPCM registry in acute PPCM and during left ventricular (LV) recovery. METHODS AND RESULTS: Clinical data including LV ejection fraction (LVEF) and Activin-A serum levels were assessed at initial diagnosis (baseline

Activin A promoted the anti-tumor effect of ActRIIA high CD8+ T cells in mouse hepatoma.

BACKGROUND: Activin A, a noteworthy member of the TGF-β superfamily. Activin A can regulate the biological functions of various immune cells, such as macrophages, neutrophils, NK cells, etc. The purpose of this study is to investigate the regulatory effect and related mechanisms of activin A on CD8+ T cells. METHODS: This study established a mouse subcutaneous transplantation model of hepatoma to explore whether activin A has a regulatory effect of CD8+ T cells. And reveal the biological characteristics of ActRIIA high CD8+ T cells. RESULTS: We discovered that CD8+ T cells express ActRIIA, A

Plasma Levels of Activin A and Follistatin-Like-3 as Biomarkers for Pulmonary Hypertension in Advanced Heart Failure.

INTRODUCTION: Pulmonary hypertension (pHTN) is a serious condition associated with increased mortality and morbidity, with limited early and non-invasive diagnostic tools. This study aimed to investigate the potential of plasma biomarkers Activin A and Follistatin-Like-3 (FSTL3) as indicators of disease severity in pHTN and right heart dysfunction. METHODS: We conducted a prospective cohort study of 120 patients with advanced heart failure undergoing right heart catheterization. Plasma levels of Activin and FSTL3 were measured at the time of the catheterization. Biomarker data was analyzed fo

Секс-хромосомное дополнение и Активин-А формируют терапевтический потенциал активации TNFR2 в модели MS и CNP.

Активация 2-го рецептора коэффициента некроза (TNFR2) является перспективной и терапевтической стратегией для аутоиммунных расстройств, таких, как множественный склероз (MS) и хроническая нейропатическая боль (CNP). Цель этого исследования заключалась в выявлении механизмов, регулирующих эффективность активации TNFR2 с точки зрения пола для снижения степени боли и моторных заболеваний у мышей, испытывающих экспериментальный аутоиммунный энцефаломиелит (EAE), который представляет собой грызуновую модель MS. Мы считаем, что ХХ-полохромосомное дополнение необходимо для сокращения связанных с EAE

Совпадение в полном тексте источника
… Activins, specifically Activin-A, are produced by male gonads and are primarily involved in spermatogenesis. However, Activin-A has also been linked to inflammation and neuropathic pain ( 36 , 37 ). … Interestingly, alleviation of CNP by TNFR2 activation is dependent on Activin-A. Activin-A is a member of Activins family and is produced by male and female gonads. The primary role of Activin is to stimulate FSH release. …

The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare and disabling genetic disorder of connective tissue characterized by congenital malformation of the great toes, and progressive heterotopic ossification (HO) in soft connective tissues. A gain-of-function mutation of activin A receptor type I (ACVR1) enables ACVR1 to recognize activin A as an agonist with bone morphogenetic protein (BMP) signalling that leads to HO. Previous studies confirmed that activin A stimulates BMP signalling in vitro and drives HO in mouse models of FOP. However, the roles for BMP4 and BMP6 in FOP

An emerging class of new therapeutics targeting TGF, Activin, and BMP ligands in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is an often fatal condition, the primary pathology of which involves loss of pulmonary vascular perfusion due to progressive aberrant vessel remodeling. The reduced capacity of the pulmonary circulation places increasing strain on the right ventricle of the heart, leading to death by heart failure. Currently, licensed therapies are primarily vasodilators, which have increased the median post-diagnosis life expectancy from 2.8 to 7 years. Although this represents a substantial improvement, the search continues for transformative therapeutics that reverse es

Activin-like kinase 5 (ALK5) inactivation in the mouse uterus results in metastatic endometrial carcinoma.

The endometrial lining of the uterine cavity is a highly dynamic tissue that is under the continuous control of the ovarian steroid hormones, estrogen and progesterone. Endometrial adenocarcinoma arises from the uncontrolled growth of the endometrial glands, which is typically associated with unopposed estrogen action and frequently occurs in older postmenopausal women. The incidence of endometrial cancer among younger women has been rising due to increasing rates of obesity, a major risk factor for the disease. The transforming growth factor β (TGFβ) family is a highly conserved group of prot

Activin A-mediated epithelial de-differentiation contributes to injury repair in an in vitro gastrointestinal reflux model.

Reflux esophagitis is a result of esophageal exposure to acid and bile during episodes of gastroesophageal reflux. Aside from chemical injury to the esophageal epithelium, it has been shown that acid and bile induce cytokine-mediated injury by stimulating the release of pro-inflammatory cytokines. During the repair and healing process following reflux injury, the squamous esophageal cells are replaced with a columnar epithelium causing Barrett's metaplasia, which predisposes patients to esophageal adenocarcinoma. We identified a novel player in gastroesophageal reflux injury, the TGFβ family m

Inhibition of activin-like kinase 4/5 attenuates cancer cachexia associated muscle wasting.

Cancer mediated activation of the ActRIIB-ALK4/5 heterodimer by myostatin is strongly associated with muscle wasting. We investigated in vitro and in vivo the efficacy of ALK4/5 receptor blockers SB431542 and GW788388 in preventing muscle wasting, and explored synergy with IGF-I analogue LONG R3 (LR3) IGF-I. In vitro, C2C12 skeletal muscle cells were treated with vehicle, SB431542, GW788388 and LR3 IGF-I. A C26-CD2F1 cachexia model was used to induce cachexia in vivo. Mice were allocated as non-tumour bearing (NTB) or C26 tumour-bearing (C26 TB) vehicle control, treated with SB431542, LR3 IGF-

Activin A-Induced Cachectic Wasting Is Attenuated by Systemic Delivery of Its Cognate Propeptide in Male Mice.

In cancer, elevated activin levels promote cachectic wasting of muscle, irrespective of tumor progression. In excess, activins A and B use the myostatin signaling pathway in muscle, triggering a decrease in protein synthesis and an increase in protein degradation, which ultimately leads to atrophy. Recently, we demonstrated that local delivery of engineered activin and myostatin propeptides (natural inhibitors of these growth factors) could induce profound muscle hypertrophy in healthy mice. Additionally, the expression of these propeptides effectively attenuated localized muscle wasting in mo…

RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice.

Over expression of hepcidin antimicrobial peptide is a common feature of iron-restricted anemia in humans. We investigated the erythroid response to either erythropoietin or RAP-011, a "murinized" ortholog of sotatercept, in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. Sotatercept, a soluble, activin receptor type IIA ligand trap, is currently being evaluated for the treatment of anemias associated with chronic renal disease, myelodysplastic syndrome, β-thalassemia, and Diamond Blackfan anemia and acts by inhibiting signaling downstream of activin and other Transf

A truncated, activin-induced Smad3 isoform acts as a transcriptional repressor of FSHβ expression in mouse pituitary.

The receptor-regulated protein Smad3 is key player in the signaling cascade stimulated by the binding of activin to its cell surface receptor. Upon phosphorylation, Smad3 forms a heterocomplex with Smad2 and Smad4, translocates to the nucleus and acts as a transcriptional co-activator. We have identified a unique isoform of Smad3 that is expressed in mature pituitary gonadotropes. 5' RACE revealed that this truncated Smad3 isoform is transcribed from an ATG site within exon 4 and consists of 7 exons encoding half of the linker region and the MH2 region. In pituitary cells, the truncated Smad3