Cerebral arteriovenous malformations. Part 1: cellular and molecular biology

2009 ◽  
Vol 26 (5) ◽  
pp. E10 ◽  
Author(s):  
Parham Moftakhar ◽  
Jason S. Hauptman ◽  
Dennis Malkasian ◽  
Neil A. Martin
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Molecular Biology ◽  
Arteriovenous Malformations ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Complex Processes ◽  
Drug Treatments ◽  
And Behavior ◽  
Endothelial Growth Factor

Object The scientific understanding of the nature of arteriovenous malformations (AVMs) in the brain is evolving. It is clear from current work that AVMs can undergo a variety of phenomena, including growth, remodeling, and/or regression—and the responsible processes are both molecular and physiological. A review of these complex processes is critical to directing future therapeutic approaches. The authors performed a comprehensive review of the literature to evaluate current information regarding the genetics, pathophysiology, and behavior of AVMs. Methods A comprehensive literature review was conducted using PubMed to reveal the molecular biology of AVMs as it relates to their complex growth and behavior patterns. Results Growth factors involved in AVMs include vascular endothelial growth factor, fibroblast growth factor, transforming growth factor β, angiopoietins, fibronectin, laminin, integrin, and matrix metalloproteinases. Conclusions Understanding the complicated molecular milieu of developing AVMs is essential for defining their natural history. Growth factors, extracellular matrix proteins, and other molecular markers will be the key to unlocking novel targeted drug treatments for these brain malformations.

VEGF, Notch and TGFβ/BMPs in regulation of sprouting angiogenesis and vascular patterning

2014 ◽  
Vol 42 (6) ◽  
pp. 1576-1583 ◽  
Author(s):  
Yi Jin ◽  
David Kaluza ◽  
Lars Jakobsson
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Vascular Patterning ◽  
Sprouting Angiogenesis ◽  
Complex Processes ◽  
Apical Side ◽  
Morphogenetic Protein ◽  
Signalling Cascades ◽  
Endothelial Growth Factor

The blood vasculature is constantly adapting to meet the demand from tissue. In so doing, branches may form, reorganize or regress. These complex processes employ integration of multiple signalling cascades, some of them being restricted to endothelial and mural cells and, hence, suitable for targeting of the vasculature. Both genetic and drug targeting experiments have demonstrated the requirement for the vascular endothelial growth factor (VEGF) system, the Delta-like–Notch system and the transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) cascades in vascular development. Although several of these signalling cascades in part converge into common downstream components, they differ in temporal and spatial regulation and expression. For example, the pro-angiogenic VEGFA is secreted by cells in need of oxygen, presented to the basal side of the endothelium, whereas BMP9 and BMP10 are supplied via the bloodstream in constant interaction with the apical side to suppress angiogenesis. Delta-like 4 (DLL4), on the other hand, is provided as an endothelial membrane bound ligand. In the present article, we discuss recent data on the integration of these pathways in the process of sprouting angiogenesis and vascular patterning and malformation.

Expression and Role of Peptides, Proteins and Growth Factors in the Pathogenesis of Endometriosis

2009 ◽  
Vol 1 (2) ◽  
pp. 79-93 ◽  
Author(s):  
Pasquale Florio ◽  
Serena Pinzauti ◽  
Aldo Altomare ◽  
Stefano Luisi ◽  
Pietro Litta ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Regulatory Peptides ◽  
Transforming Growth Factor Β ◽  
Insulin Like Growth Factor ◽  
Corticotrophin Releasing Factor ◽  
Relevant Role ◽  
Cellular And Humoral Immunity ◽  
Endothelial Growth Factor

Growing evidence is demonstrating that several peptides (corticotrophin-releasing factor, urocortins, ghrelin), proteins (leptin, adiponectin) and growth factors (vascular endothelial growth factor; epidermal growth factor family of growth factors and receptors, fibroblast growth factor, insulin like growth factor and insulin like growth factor-binding proteins, transforming growth factor-β and, activin A and related proteins) are expressed in endometriotic implants, and locally play a relevant role in affecting the biological mechanisms leading to endometriosis. They establish a complex network of interactions by which they are therefore able to stimulate angiogenesis, inflammatory cell recruitment and reaction, the growth of endometriotic tissue and its survival through the modulation of the narrow immune system. This review will evaluate the role played by several regulatory peptides, proteins and growth factors in affecting endometrial physiology and the putative mechanisms advocated to explain endometriosis (angiogenesis, cellular and humoral immunity, inflammatory response, endometrial cell proliferation, activation, motility, adhesion and invasion).

Vascular Endothelial Growth Factor Level Correlates With Transforming Growth Factor-β Isoform Levels in Pleural Effusions

CHEST Journal ◽  
2000 ◽  
Vol 118 (6) ◽  
pp. 1747-1753 ◽  
Author(s):  
Dong-sheng Cheng ◽  
Y. C. Gary Lee ◽  
Jeffrey T. Rogers ◽  
Elizabeth A. Perkett ◽  
J. Philip Moyers ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Vascular Endothelial ◽  
Pleural Effusions ◽  
Factor Level ◽  
Endothelial Growth Factor

Metalloproteinase and growth factor interactions: do they play a role in pulmonary fibrosis?

2002 ◽  
Vol 283 (1) ◽  
pp. L1-L11 ◽  
Author(s):  
Margaret K. Winkler ◽  
John L. Fowlkes
Keyword(s):  
Acute Lung Injury ◽  
Growth Factors ◽  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Inflammatory Cells ◽  
Transforming Growth Factor Β ◽  
Target Cells

Chronic lung disease due to interstitial fibrosis can be a consequence of acute lung injury and inflammation. The inflammatory response is mediated through the migration of inflammatory cells, actions of proinflammatory cytokines, and the secretion of matrix-degrading proteinases. After the initial inflammatory insult, successful healing of the lung may occur, or alternatively, dysregulated tissue repair can result in scarring and fibrosis. On the basis of recent insights into the mechanisms underlying acute lung injury and its long-term consequences, data suggest that proteinases, such as the matrix metalloproteinases (MMPs), may not only be involved in the breakdown and remodeling that occurs during the injury but may also cause the release of growth factors and cytokines known to influence growth and differentiation of target cells within the lung. Through the release of and activation of fibrosis-promoting cytokines and growth factors such as transforming growth factor-β1, tumor necrosis factor-α, and insulin-like growth factors by MMPs, we propose that these metalloproteinases may be integral to the initiation and progression of pulmonary fibrosis.

Anterior Diffuse Retinoblastoma: Mutational Analysis and Immunofluorescence Staining

2009 ◽  
Vol 133 (8) ◽  
pp. 1215-1218
Author(s):  
Michelle B. Crosby ◽  
G. Baker Hubbard ◽  
Brenda L. Gallie ◽  
Hans E. Grossniklaus
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mutational Analysis ◽  
Hypoxia Inducible Factor ◽  
Transforming Growth Factor Β ◽  
Immunofluorescence Staining ◽  
Vascular Endothelial ◽  
Factor Α ◽  
Oxide Synthase ◽  
Endothelial Growth Factor

Abstract Retinoblastoma is the most common primary intraocular tumor of childhood and may be heritable or occur sporadically. Anterior diffuse retinoblastoma is an uncommon variant that is thought to be sporadic. We describe a child with anterior diffuse retinoblastoma who presented with a pseudohypopyon. Genetic analysis showed a germline mutation of the RB1 allele that is potentially heritable. Immunofluorescence staining was positive for transforming growth factor β and for vascular endothelial growth factor and negative for inducible nitric oxide synthase and for hypoxia inducible factor α in the tumor seeds, indicating acquisition of nonischemia-mediated survival factors of the tumor seeds in the aqueous humor.

Prognostic significance of tumor angiogenesis in epithelial ovarian cancer: in association with transforming growth factor β and vascular endothelial growth factor

2004 ◽  
Vol 14 (1) ◽  
pp. 82-88
Author(s):  
M. SÖNMEZER ◽  
M. GÜNGÖR ◽  
A. Ensari ◽  
F. Ortaç
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Epithelial Ovarian Cancer ◽  
Transforming Growth Factor ◽  
Prognostic Significance ◽  
Transforming Growth Factor Β ◽  
Vascular Endothelial ◽  
Clinicopathologic Factors ◽  
Endothelial Growth Factor

We aimed to evaluate the prognostic significance of microvessel density (MVD), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGFβ), as well as to find out the relationship between MVD, and VEGF and TGFβ in epithelial ovarian cancer (EOC). Surgical specimens of 47 patients with stage I–IV primary EOC, who underwent extended surgical staging according to FIGO, were investigated. Five-μm thick tissue sections were immunostained with antibody to factor VIII-related antigen, and MVD was assessed at three separate areas of ×200 magnification. Expressions for VEGF and TGFβ were evaluated by immunohistochemical staining using related monoclonal antibodies. Results were correlated with clinicopathologic factors and survival. We did not find any correlation between MVD and clinicopathologic factors, or patient survival. Similarly, there was no association between the degree of VEGF staining and survival or clinicopathologic factors, except preoperative ascites volume, which was higher in patients showing moderate and intense VEGF staining than those with weak VEGF staining (P = 0.052). The expression of TGFβ was inversely correlated with preoperative CA-125 levels (P < 0.05). Furthermore, there was no correlation between MVD and the staining intensity of VEGF or TGFβ. In conclusion, angiogenesis does not appear as a prognostic factor in EOC. We suggest that VEGF is an important mediator of ascites formation, and that TGFβ, which is supposed to have tissue-specific actions in tumorigenesis, may have growth-inhibitory functions in EOC.

TGF-β and CTGF have overlapping and distinct fibrogenic effects on human renal cells

2002 ◽  
Vol 283 (4) ◽  
pp. F707-F716 ◽  
Author(s):  
Elizabeth Gore-Hyer ◽  
Daniel Shegogue ◽  
Malgorzata Markiewicz ◽  
Shianlen Lo ◽  
Debra Hazen-Martin ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Potent Inducer ◽  
Collagen Promoter

Transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) are ubiquitously expressed in various forms of tissue fibrosis, including fibrotic diseases of the kidney. To clarify the common and divergent roles of these growth factors in the cells responsible for pathological extracellular matrix (ECM) deposition in renal fibrosis, the effects of TGF-β and CTGF on ECM expression in primary human mesangial (HMCs) and human proximal tubule epithelial cells (HTECs) were studied. Both TGF-β and CTGF significantly induced collagen protein expression with similar potency in HMCs. Additionally, α2(I)-collagen promoter activity and mRNA levels were similarly induced by TGF-β and CTGF in HMCs. However, only TGF-β stimulated collagenous protein synthesis in HTECs. HTEC expression of tenascin-C (TN-C) was increased by TGF-β and CTGF, although TGF-β was the more potent inducer. Thus both growth factors elicit similar profibrogenic effects on ECM production in HMCs, while promoting divergent effects in HTECs. CTGF induction of TN-C, a marker of epithelial-mesenchymal transdifferentiation (EMT), with no significant induction of collagenous protein synthesis in HTECs, may suggest a more predominant role for CTGF in EMT rather than induction of excessive collagen deposition by HTECs during renal fibrosis.

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