scholarly journals Multiplexed digital quantification of binge-like alcohol-mediated alterations in maternal uterine angiogenic mRNA transcriptome

2012 ◽  
Vol 44 (11) ◽  
pp. 622-628 ◽  
Author(s):  
Jayanth Ramadoss ◽  
Ronald R. Magness

Genomic studies on fetal alcohol spectrum disorders (FASD) have utilized either genome-wide microarrays/bioinformatics or targeted real-time PCR (RT-PCR). We utilized herein for the first time a novel digital approach with high throughput as well as the capability to focus on one physiological system. The aim of the present study was to investigate alcohol-induced alterations in uterine angiogenesis-related mRNA abundance using digital mRNA technology. Four biological and three technical replicates of uterine arterial endothelial cells from third-trimester ewes were fluorescence-activated cell sorted, validated, and treated without or with binge-like alcohol. A capture probe covalently bound to an oligonucleotide containing biotin and a color-coded reporter probe were designed for 85 angiogenesis-related genes and analyzed with the Nanostring nCounter system. Twenty genes were downregulated (↓) and two upregulated (↑), including angiogenic growth factors/receptors (↓placental growth factor), adhesion molecules (↓angiopoietin-like-3; ↓collagen-18A1; ↓endoglin), proteases/matrix proteins/inhibitors (↓alanyl aminopeptidase; ↓collagen-4A3; ↓heparanase; ↓plasminogen, ↑plasminogen activator urokinase; ↓platelet factor-4; ↓plexin domain containing-1; ↓tissue inhibitor of metalloproteinases-3), transcription/signaling molecules (↓heart and neural crest derivatives-2; ↓DNA-binding protein inhibitor; ↓NOTCH-4; ↓ribosomal protein-L13a1; ↓ribosomal protein large-P1), cytokines/chemokines (↓interleukin-1B), and miscellaneous growth factors (↓leptin; ↓platelet-derived growth factor-α); ↓transforming growth factor (TGF-α; ↑TGF-β receptor-1). These novel data show significant detrimental alcohol effects on genes controlling angiogenesis supporting a mechanistic role for abnormal uteroplacental vascular development in FASD. The tripartite digital gene expression system is therefore a valuable tool to answer many additional questions about FASD from both mechanistic as well as ameliorative perspectives.

2004 ◽  
Vol 128 (1) ◽  
pp. 68-70
Author(s):  
Yun-Cai Cai ◽  
Victor Roggli ◽  
Eugene Mark ◽  
Philip T. Cagle ◽  
Armando E. Fraire

Abstract Background.—Growth factors such as transforming growth factor α (TGF-α) and epidermal growth factor receptor (EGFR) play an important role in cell proliferation. The immunohistochemical expression of these factors has been extensively studied in malignant tumors including mesothelioma. However, the comparative expression of these growth factors in mesothelioma and reactive mesothelial proliferations has been less well studied. Objective.—To evaluate the possible role of TGF-α and EGFR in the clinically important distinction between reactive mesothelial proliferations and malignant mesothelioma. Methods.—The expression of TGF-α and EGFR was studied in 39 cases of mesothelioma and 30 cases of reactive mesothelial proliferations by means of immunohistochemistry. Results.—Fourteen (70%) of 20 reactive mesothelial proliferations tested and 29 (76%) of 38 mesotheliomas tested expressed TGF-α. One (3%) of 30 reactive mesothelial proliferations and 17 (45%) of 39 mesotheliomas expressed EGFR. Conclusions.—These results suggest an up-regulation of EGFR in mesothelioma as compared with reactive mesothelial proliferations. This up-regulation further suggests a possible use of EGFR as an adjunct immunohistochemical test in the differential diagnosis of mesothelioma and reactive mesothelial proliferations.


1992 ◽  
Vol 101 (4) ◽  
pp. 349-354 ◽  
Author(s):  
David B. Hom ◽  
Robert H. Maisel

Since their discovery 30 years ago, angiogenic growth factors have been demonstrated to stimulate neovascularization in vitro and in animal studies. Over the last decade, knowledge gained in the field of angiogenic growth factors has grown immensely. These angiogenic growth factors exist in four major families: fibroblast growth factor (FGF), transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF). Each has the ability to induce soft tissue vascularization in microgram quantities. In animal models, FGF, TGF-β, PDGF, and EGF have been shown to enhance soft tissue wound healing. In human clinical trials, EGF and a mixture of PDGFs have been demonstrated to accelerate epidermal regeneration in cutaneous wounds. These factors have considerable therapeutic potential in the areas of soft tissue wound healing and otolaryngology. This article reviews important aspects of angiogenic growth factors and discusses their future potential in soft tissue wound healing.


MRS Bulletin ◽  
1996 ◽  
Vol 21 (11) ◽  
pp. 62-65 ◽  
Author(s):  
W. Mark Saltzman

Soluble signaling proteins called growth factors execute critical functions during the formation of specialized tissues throughout the developing embryo. When growth factors are provided to adult animals, they often encourage regeneration or repair of organs damaged by disease or trauma: Basic fibroblast growth factor (bFGF) and transforming growth factor ß1 (TGF-ß1) encourage wound healing hematopoetic growth factors stimulate the production of blood cells, bone morphogenetic proteins (BMPs) induce bone formation, nerve growth factor (NGF) enhances the survival of degenerating cholinergic neurons, and angiogenic growth factors activate new blood-vessel growth. Our understanding of the role of growth factors in development and regeneration should continue to expand dramatically over the next decade, inasmuch as new molecules (and new activities for known molecules) are appearing at a rapid rate.Protein growth factors may be useful in augmenting the new approaches for tissue engineering. Modern biotechnology permits the large-scale manufacture of highly purified proteins so that large quantities can be produced for use in humans. However proteins are often exceedingly difficult to administer, particularly if sustained levels are required. Most protein growth factors have short half-lives after intravenous injection, with their biological activity lasting only a few minutes in the circulation, so that injection must be repeated frequently to obtain sustained blood levels (Table I). Since these molecules are large, they penetrate tissue barriers, such as the capillary wall, very slowly. In addition, growth factors are extremely potent, often possessing biological activity at a number of tissue sites throughout the body. Therefore systemic administration can lead to toxicity. In view of these difficulties, new methods for growth-factor delivery are needed. The most promising new methods involve polymers, which can be engineered to provide precisely controlled, prolonged growth-factor delivery at a localized site.


1996 ◽  
Vol 320 (2) ◽  
pp. 659-664 ◽  
Author(s):  
Marianne MADLENER ◽  
Cornelia MAUCH ◽  
Walter CONCA ◽  
Maria BRAUCHLE ◽  
William C. PARKS ◽  
...  

Keratinocyte growth factor (KGF) has been implicated in wound re-epithelialization and branching morphogenesis of several organs. To determine whether KGF induces these effects via induction of matrix metalloproteinase expression we have analysed the effect of KGF on the expression of stromelysin-2 in cultured HaCaT keratinocytes. Here we show a strong induction of stromelysin-2 mRNA within 5–8 h of stimulation of these cells with KGF. The degree of induction was similar to that achieved by treatment with epidermal growth factor or tumour necrosis factor α, whereas the stimulatory effect of transforming growth factor β1 was even stronger. To determine whether the induction of stromelysin-2 expression by growth factors and cytokines might be important for wound healing, we analysed the expression of this gene during the healing process of full-thickness excisional wounds in mice. Whereas stromelysin-2 mRNA could hardly be detected in unwounded skin, a biphasic induction was seen after injury and highest levels were found at days 1 and 5 after wounding. Hybridization in situ revealed the presence of stromelysin-2 mRNA in basal keratinocytes at the wound edge but not in the underlying mesenchymal tissue. During impaired wound healing as seen in glucocorticoid-treated mice, stromelysin-2 expression was significantly increased compared with untreated control mice. Taken together, these results suggest that correct regulation of this broad-spectrum metalloproteinase might be important for normal repair.


2020 ◽  
Vol 21 (19) ◽  
pp. 7267
Author(s):  
Elena Stocco ◽  
Silvia Barbon ◽  
Cinzia Tortorella ◽  
Veronica Macchi ◽  
Raffaele De Caro ◽  
...  

The carotid body may undergo plasticity changes during development/ageing and in response to environmental (hypoxia and hyperoxia), metabolic, and inflammatory stimuli. The different cell types of the carotid body express a wide series of growth factors and corresponding receptors, which play a role in the modulation of carotid body function and plasticity. In particular, type I cells express nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor, insulin-like-growth factor-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-α and -β, interleukin-1β and -6, tumor necrosis factor-α, vascular endothelial growth factor, and endothelin-1. Many specific growth factor receptors have been identified in type I cells, indicating autocrine/paracrine effects. Type II cells may also produce growth factors and express corresponding receptors. Future research will have to consider growth factors in further experimental models of cardiovascular, metabolic, and inflammatory diseases and in human (normal and pathologic) samples. From a methodological point of view, microarray and/or proteomic approaches would permit contemporary analyses of large groups of growth factors. The eventual identification of physical interactions between receptors of different growth factors and/or neuromodulators could also add insights regarding functional interactions between different trophic mechanisms.


2021 ◽  
Vol 15 (1) ◽  
pp. 87-93
Author(s):  
S. V. Maglevaniy ◽  
E. A. Naryshkin ◽  
E. V. Chetina ◽  
M. A. Makarov

The paper reviews the data available in the literature on the mechanisms of action of platelet-rich plasma (PRP) and the experience of its use in patients with rheumatoid arthritis (RA). It defines the place of PRP in the systemic and local therapy of RA. The chemical composition of PRP and the structure of the platelet organelles included in it are described. An estimate is made for procedures to prepare platelet-rich plasma containing different concentrations of key growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor α (TGFα), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), and epidermal growth factor (EGF). The variants of PRP classifications, which take into account differences in the composition and levels of the growth factors, are considered. The experience with intra-articular injections of autologous plasma products in patients with RA and synovitis is analyzed. These findings lead to the conclusion that PRP therapy can be an effective tool to relieve inflammation and to stimulate local reparative processes in damaged joint tissues in patients with RA. Further study of the possibilities of using this method of therapy and the formation of a PRPtherapy protocol for patients with rheumatoid arthritis will provide effective personalized care to these patients.


Sign in / Sign up

Export Citation Format

Share Document