scholarly journals Somite morphogenesis is required for axial blood vessel formation

2021 ◽  
Author(s):  
Eric Paulissen ◽  
Joshua S. Waxman ◽  
Benjamin L. Martin
Keyword(s):  
Retinoic Acid ◽  
Blood Vessels ◽  
Critical Role ◽  
Physical Space ◽  
Cardinal Vein ◽  
Ventral Midline ◽  
Blood Vessel Formation ◽  
Final Destination ◽  
Summary Statement ◽  
Shape Changes

ABSTRACTAngioblasts that form the major axial blood vessels of the dorsal aorta and cardinal vein migrate towards the embryonic midline from distant lateral positions. Little is known about what controls the precise timing of angioblast migration and their final destination at the midline. Using zebrafish, we found that midline angioblast migration requires neighboring tissue rearrangements generated by somite morphogenesis. The somitic shape changes cause the adjacent notochord to separate from the underlying endoderm, creating a ventral midline cavity that provides a physical space for the angioblasts to migrate into. The anterior to posterior progression of midline angioblast migration is facilitated by retinoic acid induced anterior to posterior somite maturation and the subsequent progressive opening of the ventral midline cavity. Our work demonstrates a critical role for somite morphogenesis in organizing surrounding tissues to facilitate notochord positioning and angioblast migration, which is ultimately responsible for creating a functional cardiovascular system.Summary statementRetinoic acid induced somite morphogenesis generates a midline cavity that accommodates migrating angioblasts, which form the axial blood vessels.

scholarly journals Effect of ginger extract on angiogenesis using CAM assay

2017 ◽  
Vol 12 (3) ◽  
pp. 348 ◽  
Author(s):  
Muhammad Farhan Bashir ◽  
Muhammad Imran Qadir
Keyword(s):  
Blood Vessels ◽  
Critical Role ◽  
Video Clip ◽  
Cam Assay ◽  
Ginger Extract ◽  
Angiogenic Activity ◽  
Blood Vessel Formation ◽  
Pathological Conditions ◽  
Full Screen ◽  
Different Doses

<p>Angiogenesis performs a critical role in the embryonic growth and several pathological conditions in cancer. This study evaluated the anti-angiogenic properties of the ginger extract using CAM assay. Ginger extract was prepared by methanol. Window was made after 5 days of incubation of eggs and the ginger extract was applied on day 6 at different doses (20, 50, 75 and 150 µL). SPIP software was utilized to investigate the CAM region and diameter of blood vessels. Ginger extract proved anti-angiogenic cones-quence by decreasing the diameter of CAM of blood vessels. Comparable results were attained at dilution of 150 µL. The anti-angiogenic activity of ginger extract implicates its possible application for diseases where inhibition of blood vessel formation is desired.</p><p><strong>Video Clip of Methodology</strong>:</p><p>7 min 32 sec:   <a href="https://www.youtube.com/v/ZUY2cY09Otg">Full screen</a>   <a href="https://www.youtube.com/watch?v=ZUY2cY09Otg">Alternate</a> </p>

The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells

Blood ◽  
2005 ◽  
Vol 105 (5) ◽  
pp. 1916-1922 ◽  
Author(s):  
Steven M. Guthrie ◽  
Lisa M. Curtis ◽  
Robert N. Mames ◽  
Gregory G. Simon ◽  
Maria B. Grant ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Blood Vessel ◽  
Blood Vessels ◽  
Critical Role ◽  
Mouse Retina ◽  
Hematopoietic Stem ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Oxide Synthase

AbstractWe have previously established a model inducing hematopoietic stem cell (HSC) production of circulating endothelial progenitor cells (EPCs) to revascularize ischemic injury in adult mouse retina. The unique vascular environment of the retina results in new blood vessel formation primarily from HSC-derived EPCs. Using mice deficient (–/–) in inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), we show that vessel phenotype resulting from hemangioblast activity can be altered by modulation of the NO/NOS pathway. iNOS–/– or eNOS–/– animals were engrafted with wild-type (WT) HSCs expressing green fluorescence protein (gfp+) and subjected to our adult retinal ischemia model. WT hemangioblast activity in adult iNOS–/– recipients resulted in the formation of highly branched blood vessels of donor origin, which were readily perfused indicating functionality. In contrast, eNOS–/– recipients produced relatively unbranched blood vessels with significant donor contribution that were difficult to perfuse, indicating poor functionality. Furthermore, eNOS–/– chimeras had extensive gfp+ HSC contribution throughout their vasculature without additional injury. This neovascularization, via EPCs derived from the transplanted HSCs, reveals that the NO pathway can modulate EPC activity and plays a critical role in both blood vessel formation in response to injury and normal endothelial cell maintenance.

Effect of all-trans retinoic acid and pentagalloyl glucose on smooth muscle cell elastogenesis

2021 ◽  
pp. 1-13
Author(s):  
Kaveh Sanaei ◽  
Sydney Plotner ◽  
Anson Oommen Jacob ◽  
Jaime Ramirez-Vick ◽  
Narendra Vyavahare ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Retinoic Acid ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Muscle Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Tissue Engineered Blood Vessels ◽  
Pentagalloyl Glucose ◽  
Vitamin A Derivative

BACKGROUND: The main objective of tissue engineering is to fabricate a tissue construct that mimics native tissue both biologically and mechanically. A recurring problem for tissue-engineered blood vessels (TEBV) is deficient elastogenesis from seeded smooth muscle cells. Elastin is an integral mechanical component in blood vessels, allowing elastic deformation and retraction in response to the shear and pulsatile forces of the cardiac system. OBJECTIVE: The goal of this research is to assess the effect of the vitamin A derivative all-trans retinoic acid (RA) and polyphenol pentagalloyl glucose (PGG) on the expression of elastin in human aortic smooth muscle cells (hASMC). METHODS: A polycaprolactone (PCL) and the gelatin polymer composite was electrospun and doped with RA and PGG. The scaffolds were subsequently seeded with hASMCs and incubated for five weeks. The resulting tissue-engineered constructs were evaluated using qPCR and Fastin assay for their elastin expression and deposition. RESULTS: All treatments showed an increased elastin expression compared to the control, with PGG treatments showing a significant increase in gene expression and elastin deposition.

scholarly journals Orphan Receptor COUP-TF Is Required for Induction of Retinoic Acid Receptor β, Growth Inhibition, and Apoptosis by Retinoic Acid in Cancer Cells

2000 ◽  
Vol 20 (3) ◽  
pp. 957-970 ◽  
Author(s):  
Bingzhen Lin ◽  
Guo-quan Chen ◽  
Dongmei Xiao ◽  
Siva Kumar Kolluri ◽  
Xihua Cao ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Retinoic Acid Receptor ◽  
Critical Role ◽  
Orphan Receptor ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Transient Transfection Assay ◽  
Acid Receptor

ABSTRACT Retinoic acid receptor β (RARβ) plays a critical role in mediating the anticancer effects of retinoids. Expression of RARβ is highly induced by retinoic acid (RA) through a RA response element (βRARE) that is activated by heterodimers of RARs and retinoid X receptors (RXRs). However, RARβ induction is often lost in cancer cells despite expression of RARs and RXRs. In this study, we provide evidence that orphan receptor COUP-TF is required for induction of RARβ expression, growth inhibition, and apoptosis by RA in cancer cells. Expression of COUP-TF correlates with RARβ induction in a variety of cancer cell lines. In addition, stable expression of COUP-TF in COUP-TF-negative cancer cells restores induction of RARβ expression, growth inhibition, and apoptosis by RA, whereas inhibition of COUP-TF by expression of COUP-TF antisense RNA represses the RA effects. In a transient transfection assay, COUP-TF strongly induced transcriptional activity of the RARβ promoter in a RA- and RARα-dependent manner. By mutation analysis, we demonstrate that the effect of COUP-TF requires its binding to a DR-8 element present in the RARβ promoter. The binding of COUP-TF to the DR-8 element synergistically increases the RA-dependent RARα transactivation function by enhancing the interaction of RARα with its coactivator CREB binding protein. These results demonstrate that COUP-TF, by serving as an accessory protein for RARα to induce RARβ expression, plays a critical role in regulating the anticancer activities of retinoids.

scholarly journals Unraveling the physiological roles of retinoic acid receptor-related orphan receptor α

2021 ◽  
Author(s):  
Ji Min Lee ◽  
Hyunkyung Kim ◽  
Sung Hee Baek
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Metabolic Diseases ◽  
Retinoic Acid Receptor ◽  
Critical Role ◽  
Orphan Receptor ◽  
Orphan Nuclear Receptor ◽  
Functional Link ◽  
Acid Receptor

AbstractRetinoic acid receptor-related orphan receptor-α (RORα) is a member of the orphan nuclear receptor family and functions as a transcriptional activator in response to circadian changes. Circadian rhythms are complex cellular mechanisms regulating diverse metabolic, inflammatory, and tumorigenic gene expression pathways that govern cyclic cellular physiology. Disruption of circadian regulators, including RORα, plays a critical role in tumorigenesis and facilitates the development of inflammatory hallmarks. Although RORα contributes to overall fitness among anticancer, anti-inflammatory, lipid homeostasis, and circadian clock mechanisms, the molecular mechanisms underlying the mode of transcriptional regulation by RORα remain unclear. Nonetheless, RORα has important implications for pharmacological prevention of cancer, inflammation, and metabolic diseases, and understanding context-dependent RORα regulation will provide an innovative approach for unraveling the functional link between cancer metabolism and rhythm changes.

scholarly journals (Inverse) Agonists of Retinoic Acid–Related Orphan Receptor γ: Regulation of Immune Responses, Inflammation, and Autoimmune Disease

2020 ◽  
Vol 60 (1) ◽  
pp. 371-390 ◽  
Author(s):  
Anton M. Jetten ◽  
Donald N. Cook
Keyword(s):  
Retinoic Acid ◽  
Autoimmune Disease ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Transcriptional Activity ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Critical Role ◽  
Orphan Receptor ◽  
Inverse Agonists

Retinoic acid–related orphan receptor γt (RORγt) functions as a ligand-dependent transcription factor that regulates multiple proinflammatory genes and plays a critical role in several inflammatory and autoimmune diseases. Various endogenous and synthetic RORγ (inverse) agonists have been identified that regulate RORγ transcriptional activity, including many cholesterol intermediates and oxysterols. Changes in cholesterol biosynthesis and metabolism can therefore have a significant impact on the generation of oxysterol RORγ ligands and, consequently, can control RORγt activity and inflammation. These observations contribute to a growing literature that connects cholesterol metabolism to the regulation of immune responses and autoimmune disease. Loss of RORγ function in knockout mice and in mice treated with RORγ inverse agonists results in reduced production of proinflammatory cytokines, such as IL-17A/F, and increased resistance to autoimmune disease in several experimental rodent models. Thus, RORγt inverse agonists might provide an attractive therapeutic approach to treat a variety of autoimmune diseases.

scholarly journals Bmpr1bb is a novel gene involved in retinoic acid induced patterning of the zebrafish hindbrain

Eureka ◽  
2010 ◽  
Vol 1 (1) ◽  
pp. 11-19
Author(s):  
Braden Teitge
Keyword(s):  
Retinoic Acid ◽  
Bone Morphogenetic Proteins ◽  
Critical Role ◽  
Retinoic Acid Treatment ◽  
Teratogenic Effects ◽  
Downstream Target ◽  
Retinoic Acid Signalling ◽  
Uncharacterized Gene ◽  
Vitamin A Derivative

Retinoic acid signalling plays a critical role during zebrafish development.  The teratogenic effects of retinoic acid have been demonstrated by embryonic deformation resulting from insufficient or excessive levels of this vitamin A derivative.  During embryogenesis, bone morphogenetic proteins are closely linked to the physiological interpretation of RA gradients, particularly in the hindbrain.  We describe an uncharacterized gene, Bmpr1bb, as being significantly downregulated in response to retinoic acid treatment.  In situ expression demonstrates that Bmpr1bb is expressed ubiquitously at 10hpf, and is slowly downregulated until 48hpf where the expression is concentrated in the hindbrain.  We propose that Bmpr1bb is a downstream target of RA signalling, strongly downregulated during embryogenesis and specified to a specific region of the hindbrain.

scholarly journals Retinoic acid modulation of glutathione and cysteine metabolism in chondrocytes

1996 ◽  
Vol 314 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Cristina C. TEIXEIRA ◽  
Irving M. SHAPIRO ◽  
Masashi HATORI ◽  
Ramesh RAJPUROHIT ◽  
Cameron KOCH
Keyword(s):  
Ascorbic Acid ◽  
Superoxide Dismutase ◽  
Retinoic Acid ◽  
Critical Role ◽  
Phosphate Concentration ◽  
Antioxidant Systems ◽  
Chondrocyte Maturation ◽  
Medium Components ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

The major objective of this investigation was to determine the thiol status of chondrocytes and to relate changes in the level of glutathione and cysteine to maturation of the cells as they undergo terminal differentiation. Chondrocytes were isolated from the cephalic portion of chick embryo sterna and treated with all-trans retinoic acid for one week. We found that the addition of 100 nM retinoic acid to the cultures decreased the intracellular levels of glutathione and cysteine from 6.1 to 1.6 and 0.07 to 0.01 nmol/μg DNA respectively; retinoic acid also caused a decrease in the extracellular concentration of cysteine. The decrease in chondrocyte thiols was dose and time dependent. To characterize other antioxidant systems of the sternal cell culture, the activities of catalase, glutathione reductase and superoxide dismutase were determined. Activities of all of those enzymes were high in the retinoic acid-treated cells; the conditioned medium also contained these enzymes and the cytosolic isoenzyme of superoxide dismutase. We probed the specificity of the thiol response by using immature caudal chondrocytes. Unlike the cephalic cells, retinoic acid did not change intracellular glutathione and extracellular cysteine levels, although the retinoid caused a reduction in the intracellular cysteine concentration. Finally, we explored the effect of medium components on chondrocyte thiol status. We noted that while ascorbate alone did not change cell thiol levels, it did cause a 4-fold decrease in the extracellular cysteine concentration. When retinoic acid and ascorbic acid were both present in the medium, there was a marked decrease in the level of glutathione. In contrast, the phosphate concentration of the culture medium served as a powerful modulator of both glutathione and cysteine. Results of the study clearly showed that there is a profound decrease in intracellular levels of both cysteine and glutathione and that thiol levels are responsive to ascorbic acid and the medium phosphate concentration. These findings point to a critical role for thiols in modulating events linked to chondrocyte maturation and cartilage matrix synthesis and mineralization.

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