Acute regulation of activin A and its binding protein, follistatin, in serum and tissues following lipopolysaccharide treatment of adult male mice

2012 ◽  
Vol 303 (6) ◽  
pp. R665-R675 ◽  
Author(s):  
Hui Wu ◽  
Yi Chen ◽  
Wendy R. Winnall ◽  
David J. Phillips ◽  
Mark P. Hedger
Keyword(s):  
Bone Marrow ◽  
Adult Male ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Protein Translation ◽  
Transforming Growth Factor Β ◽  
Activin A ◽  
Male Mice ◽  
Mrna Transcription ◽  
Bone Marrow Derived Cells

Activin A, a member of the transforming growth factor-β family, increases in the circulation within 1 h after administration of bacterial LPS. To clarify the origins of this rapid increase, the distribution of activin A and its binding protein, follistatin, and their production following LPS treatment, were assessed in adult male mice. In untreated mice, activin A was detectable in all 23 tissues examined, with highest mRNA expression (as measured by quantitative RT-PCR) was found in the liver, and the largest concentration of activin A protein (by ELISA) was found in the bone marrow. Likewise, follistatin mRNA and protein were present in all tissues, with highest expression in the vas deferens. Activin A and follistatin mRNA did not increase significantly in any tissue within the first hour after LPS, but activin A protein decreased by 35% in the bone marrow and increased 5-fold in the lung. No significant changes were observed in any other tissue. Activin A reached a peak in the circulation 1 h following LPS, and then declined. Cycloheximide, an inhibitor of protein translation, reduced this increase of activin A by more than 50%. Actinomycin D, an inhibitor of mRNA transcription, had no effect. Circulating follistatin did not increase until 4 h after LPS and was not affected by either inhibitor. These data indicate that the rapid increase in circulating activin A during LPS-induced inflammation is regulated at the posttranscriptional level, apparently from newly translated and stored protein, and implicate bone marrow-derived cells, and, in particular, neutrophils, as a significant source of this preformed activin A.

scholarly journals Angiogenic Recruitment of Pericytes from Bone Marrow after Stroke

2005 ◽  
Vol 26 (4) ◽  
pp. 545-555 ◽  
Author(s):  
Erzsebet Kokovay ◽  
Lu Li ◽  
Lee A Cunningham
Keyword(s):  
Bone Marrow ◽  
Cerebral Ischemia ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Fluorescent Protein ◽  
Transforming Growth Factor Β ◽  
Brain Parenchyma ◽  
Specific Marker ◽  
Bone Marrow Derived Cells ◽  
The Brain

Bone marrow-derived cells (BMDCs) contribute to revascularization after ischemia. However, the mechanisms by which BMDCs support vessel remodeling after cerebral ischemia are not clear. Using mouse chimeras that express enhanced green fluorescent protein in reconstituted bone marrow, we investigated the role of BMDCs in revascularization and brain repair after middle cerebral artery occlusion of murine brain. After ischemia, two populations of BMDCs were observed, one in the brain parenchyma and another associated with the vasculature. The number of BMDCs that infiltrated the brain parenchyma peaked at 7 days and persisted through 14 days, the last time point observed. The majority of BMDCs were characterized as microglia, based on cell-type-specific marker expression. We observed a robust angiogenic response after cerebral ischemia. Bone marrow-derived cells associated with remodeling blood vessels were negative for endothelial markers, but were surrounded by basal lamina and expressed desmin and vimentin, identifying these cells as pericytes. Quantification of BMDCs that expressed desmin revealed increasing desmin expression with time. Perivascular associated BMDCs that expressed desmin were immunoreactive for the angiogenic factors vascular endothelial growth factor and transforming growth factor- β. These findings suggest that pericytes are recruited from the periphery and are involved in blood vessel stabilization during ischemiainduced angiogenesis.

Versican G1 and G3 domains are upregulated and latent transforming growth factor-β binding protein-4 is downregulated in breast cancer stroma

Breast Cancer ◽  
2011 ◽  
Vol 19 (1) ◽  
pp. 46-53 ◽  
Author(s):  
Yuko Takahashi ◽  
Hiroko Kuwabara ◽  
Masahiko Yoneda ◽  
Zenzo Isogai ◽  
Nobuhiko Tanigawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Transforming Growth Factor Β ◽  
Cancer Stroma

scholarly journals SARP, a new alternatively spliced protein phosphatase 1 and DNA interacting protein

2007 ◽  
Vol 402 (1) ◽  
pp. 187-196 ◽  
Author(s):  
Gareth J. Browne ◽  
Margarida Fardilha ◽  
Senga K. Oxenham ◽  
Wenjuan Wu ◽  
Nicholas R. Helps ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Mammalian Cells ◽  
Leucine Zipper ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Transforming Growth Factor Β ◽  
Ankyrin Repeat ◽  
Protein Phosphatase 1 ◽  
Binding Motif ◽  
Alternative Mrna Splicing

PP1 (protein phosphatase 1) is a ubiquitously expressed serine/threonine-specific protein phosphatase whose activity towards different substrates appears to be mediated via binding to specific proteins that play critical regulatory and targeting roles. In the present paper we report the cloning and characterization of a new protein, termed SARP (several ankyrin repeat protein), which is shown to interact with all isoforms of PP1 by a variety of techniques. A region encompassing a consensus PP1-binding motif in SARP (K354VHF357) modulates endogenous SARP–PP1 activity in mammalian cells. This SARP–PP1 interaction motif lies partially within the first ankyrin repeat in contrast with other proteins [53BP2 (p53 binding protein 2), MYPT1/M110/MBS (myosin binding protein of PP1) and TIMAP (transforming growth factor β inhibited, membrane-associated protein)], where a PP1-binding motif precedes the ankyrin repeats. Alternative mRNA splicing produces several isoforms of SARP from a single human gene at locus 11q14. SARP1 and/or SARP2 (92–95 kDa) are ubiquitously expressed in all tissues with high levels in testis and sperm, where they are shown to interact with both PP1γ1 and PP1γ2. SARP3 (65 kDa) is most abundant in brain where SARP isoforms interact with both PP1α and PP1γ1. SARP is highly abundant in the nucleus of mammalian cells, consistent with the putative nuclear localization signal at the N-terminus. The presence of a leucine zipper near the C-terminus of SARP1 and SARP2, and the binding of mammalian DNA to SARP2, suggests that SARP1 and SARP2 may be transcription factors or DNA-associated proteins that modulate gene expression.

scholarly journals Temporal transcriptomic profiling reveals dynamic changes in gene expression of Xenopus animal cap upon activin treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumeko Satou-Kobayashi ◽  
Jun-Dal Kim ◽  
Akiyoshi Fukamizu ◽  
Makoto Asashima
Keyword(s):  
Time Course ◽  
Transforming Growth Factor ◽  
Transcriptome Profiling ◽  
Transforming Growth Factor Β ◽  
Activin A ◽  
Cytokine Signaling ◽  
Molecular Characteristics ◽  
Transcriptional Dynamics

AbstractActivin, a member of the transforming growth factor-β (TGF-β) superfamily of proteins, induces various tissues from the amphibian presumptive ectoderm, called animal cap explants (ACs) in vitro. However, it remains unclear how and to what extent the resulting cells recapitulate in vivo development. To comprehensively understand whether the molecular dynamics during activin-induced ACs differentiation reflect the normal development, we performed time-course transcriptome profiling of Xenopus ACs treated with 50 ng/mL of activin A, which predominantly induced dorsal mesoderm. The number of differentially expressed genes (DEGs) in response to activin A increased over time, and totally 9857 upregulated and 6663 downregulated DEGs were detected. 1861 common upregulated DEGs among all Post_activin samples included several Spemann’s organizer genes. In addition, the temporal transcriptomes were clearly classified into four distinct groups in correspondence with specific features, reflecting stepwise differentiation into mesoderm derivatives, and a decline in the regulation of nuclear envelop and golgi. From the set of early responsive genes, we also identified the suppressor of cytokine signaling 3 (socs3) as a novel activin A-inducible gene. Our transcriptome data provide a framework to elucidate the transcriptional dynamics of activin-driven AC differentiation, reflecting the molecular characteristics of early normal embryogenesis.

scholarly journals Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2070
Author(s):  
Pasquale Esposito ◽  
Daniela Verzola ◽  
Daniela Picciotto ◽  
Leda Cipriani ◽  
Francesca Viazzi ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Vascular Inflammation ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Activin A ◽  
Premature Aging ◽  
High Morbidity ◽  
Type I

A current hypothesis is that transforming growth factor-β signaling ligands, such as activin-A and myostatin, play a role in vascular damage in atherosclerosis and chronic kidney disease (CKD). Myostatin and activin-A bind with different affinity the activin receptors (type I or II), activating distinct intracellular signaling pathways and finally leading to modulation of gene expression. Myostatin and activin-A are expressed by different cell types and tissues, including muscle, kidney, reproductive system, immune cells, heart, and vessels, where they exert pleiotropic effects. In arterial vessels, experimental evidence indicates that myostatin may mostly promote vascular inflammation and premature aging, while activin-A is involved in the pathogenesis of vascular calcification and CKD-related mineral bone disorders. In this review, we discuss novel insights into the biology and physiology of the role played by myostatin and activin in the vascular wall, focusing on the experimental and clinical data, which suggest the involvement of these molecules in vascular remodeling and calcification processes. Moreover, we describe the strategies that have been used to modulate the activin downward signal. Understanding the role of myostatin/activin signaling in vascular disease and bone metabolism may provide novel therapeutic opportunities to improve the treatment of conditions still associated with high morbidity and mortality.

Latent transforming growth factor-β binding protein-1 LTBP1

1998 ◽  
pp. 178-180
Author(s):  
Shirley Ayad ◽  
Ray Boot-Handford ◽  
Martin J. Humphries ◽  
Karl E. Kadler ◽  
Adrian Shuttleworth
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Transforming Growth Factor Β
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