scholarly journals Clinical progression and familial occurrence of cerebral cavernous angiomas: the role of angiogenic and growth factors

2006 ◽  
Vol 21 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Francesco Maiuri ◽  
Paolo Cappabianca ◽  
Michelangelo Gangemi ◽  
Marialaura Del Basso De Caro ◽  
Felice Esposito ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mass Effect ◽  
Transforming Growth Factor Β ◽  
Brain Parenchyma ◽  
Familial Occurrence ◽  
Ki 67 ◽  
Cavernous Angiomas ◽  
The Brain

Object The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors. Methods Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor–β [TGFβ], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases). The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFβ expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFβ, PDGF, and tenascin in more aggressive cavernomas. Conclusions The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.

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.

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.

Characteristics of early murine B-lymphocyte precursors and their direct sensitivity to negative regulators

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2708-2715 ◽  
Author(s):  
Taku Kouro ◽  
Kay L. Medina ◽  
Kenji Oritani ◽  
Paul W. Kincade
Keyword(s):  
B Cells ◽  
Growth Factor ◽  
B Lymphocyte ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Transforming Growth Factor Β ◽  
Ki 67 ◽  
Differentiation Potential ◽  
Murine Bone Marrow ◽  
B Lineage

Abstract Recently, a collection of surface markers was exploited to isolate viable Lin− TdT+ cells from murine bone marrow. These early pro-B cells were enriched for B-lineage lymphocyte precursor activity measured by short-term culture and had little responsiveness to myeloid growth factors. Early precursors can be propagated with remarkably high cloning frequencies in stromal cell–free, serum-free cultures, permitting this analysis of direct regulatory factors. Expression of the interleukin-7 receptor (IL-7Rα) chain marks functional precursors and IL-7 is necessary for progression beyond the CD45RA+ CD19− stage. Efficient survival and differentiation were only observed when stem cell factor and Flt-3 ligand were also present. IL-7–responsive CD19+precursors are estrogen resistant. However, B-lineage differentiation was selectively abrogated when highly purified Lin− precursors were treated with hormone in the absence of stromal cells. In addition, early stages of B lymphopoiesis were arrested by limitin, a new interferon (IFN)–like cytokine as well as IFN-α, IFN-γ, or transforming growth factor β (TGF-β), but not by epidermal growth factor (EGF). Lin− TdT+early pro-B cells are shown here to be CD27+AA4.1+/−Ki-67+ Ly-6C−Ly-6A/Sca-1Lo/−Thy-1−CD43+CD4+/−CD16/32Lo/−CD44Hi and similar in some respects to the “common lymphoid progenitors” (CLP) identified by others. Although early pro-B cells have lost myeloid differentiation potential, transplantation experiments described here reveal that at least some can generate T lymphocytes. Of particular importance is the demonstration that a pivotal early stage of lymphopoiesis is directly sensitive to negative regulation by hormones and cytokines.

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.

scholarly journals Myofibroblasts. II. Intestinal subepithelial myofibroblasts

1999 ◽  
Vol 277 (2) ◽  
pp. C183-C201 ◽  
Author(s):  
D. W. Powell ◽  
R. C. Mifflin ◽  
J. D. Valentich ◽  
S. E. Crowe ◽  
J. I. Saada ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Collagenous Colitis ◽  
Transforming Growth Factor Β ◽  
Osmotic Gradient ◽  
Paracrine Secretion ◽  
Cox 2 ◽  
Cells Of Cajal

Intestinal subepithelial myofibroblasts (ISEMF) and the interstitial cells of Cajal are the two types of myofibroblasts identified in the intestine. Intestinal myofibroblasts are activated and proliferate in response to various growth factors, particularly the platelet-derived growth factor (PDGF) family, which includes PDGF-BB and stem cell factor (SCF), through expression of PDGF receptors and the SCF receptor c- kit. ISEMF have been shown to play important roles in the organogenesis of the intestine, and growth factors and cytokines secreted by these cells promote epithelial restitution and proliferation, i.e., wound repair. Their role in the fibrosis of Crohn’s disease and collagenous colitis is being investigated. Through cyclooxygenase (COX)-1 and COX-2 activation, ISEMF augment intestinal ion secretion in response to certain secretagogues. By forming a subepithelial barrier to Na+ diffusion, they create a hypertonic compartment that may account for the ability of the gut to transport fluid against an adverse osmotic gradient. Through the paracrine secretion of prostaglandins and growth factors (e.g., transforming growth factor-β), ISEMF may play a role in colonic tumorigenesis and metastasis. COX-2 in polyp ISEMF may be a target for nonsteroidal anti-inflammatory drugs (NSAIDs), which would account for the regression of the neoplasms in familial adenomatous polyposis and the preventive effect of NSAIDs in the development of sporadic colon neoplasms. More investigation is needed to clarify the functions of these pleiotropic cells.

scholarly journals Basic Studies on the Clinical Applications of Platelet-Rich Plasma

2003 ◽  
Vol 12 (5) ◽  
pp. 509-518 ◽  
Author(s):  
Masaki Yazawa ◽  
Hisao Ogata ◽  
Tatsuo Nakajima ◽  
Taisuke Mori ◽  
Naohide Watanabe ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibrin Glue ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Transforming Growth Factor Β ◽  
Clinical Applications ◽  
Platelet Concentrate ◽  
Platelet Concentrates ◽  
Basic Studies

Platelets, which contain many growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β), are being used in clinical applications as platelet-rich plasma (PRP). Only a few studies, however, have been conducted on the growth factors present in PRP and on the clinical applications using the drug delivery system (DDS). For the purpose of clinical application, we first modified the PRP preparation method and assessed the amounts of growth factors contained in the human platelet concentrates. Furthermore, we assessed fibrin glue as a DDS of platelet concentrates. Platelet precipitations were made by twice centrifuging human whole blood. The precipitated platelet was resuspended to yield the platelet concentrates. The growth factor concentrations were measured. Fibrin glue sheets containing this platelet concentrate were implanted in rabbit pinna and samples were obtained for immunostaining (anti-PDGF antibody) to assess the use of PRP over time using the fibrin glue as the DDS. The mean concentration of growth factors present in the platelet concentrates was three times or greater than that of conventional PRP. Furthermore, the results indicated that when the platelet concentrate was used with fibrin glue as a carrier, the contents were released over a period of about 1 week. This raises the possibility that this system may be useful in clinical applications.

Regeneration neurohormones and growth factors in echinoderms

2001 ◽  
Vol 79 (7) ◽  
pp. 1171-1208 ◽  
Author(s):  
M C Thorndyke ◽  
MD Candia Carnevali
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Molecular Level ◽  
Distribution Patterns ◽  
Transforming Growth Factor Β ◽  
Regenerative Processes ◽  
Blastema Formation ◽  
Undifferentiated Cells ◽  
Growth Promoting

There has been much recent interest in the presence and biological functions of growth regulators in invertebrates. In spite of the different distribution patterns of these molecules in different phyla (from molluscs, insects, and annelids to echinoderms and tunicates), they seem always to be extensively involved in developmental processes, both embryonic and regenerative. Echinoderms are well known for their striking regenerative potential and many can completely regenerate arms that, for example, are lost following self-induced or traumatic amputation. Thus, they provide a valuable experimental model for the study of regenerative processes from the macroscopic to the molecular level. In crinoids as well as probably all ophiuroids, regeneration is rapid and occurs by means of a mechanism that involves blastema formation, known as epimorphosis, where the new tissues arise from undifferentiated cells. In asteroids, morphallaxis is the mechanism employed, replacement cells being derived from existing tissues following differentiation and (or) transdifferentiation. This paper focuses on the possible contribution of neurohormones and growth factors during both repair and regenerative processes. Three different classes of regulatory molecules are proposed as plausible candidates for growth-promoting factors in regeneration: neurotransmitters (monoamines), neuropeptides (substance P, SALMFamides 1 and 2), and growth-factor-like molecules (TGF-β (transforming growth factor β), NGF (nerve growth factor), RGF-2 (basic fibroblast growth factor)).

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