Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells.

Amento, Edward P.; Ehsani, Niloofar; Palmer, Helen J.; Libby, Peter

doi:10.1161/01.atv.11.5.1223

Cited by 525 publications

(300 citation statements)

References 49 publications

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“…6g), which was blocked by halofuginone. In line with previous reports, 31,32 pericytes strongly responded to TGFb1 stimulation. It strongly reduced proliferation and increased Col1a1 expression in a dose-dependent manner.…”

Section: Halofuginone Affects Proliferation Of Pericytes In Vitrosupporting

confidence: 93%

Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

Kempen

Rijntjes

Mamor-Cornelissen

et al. 2007

Intl Journal of Cancer

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Tumors are complex tissues composed of neoplastic cells, soluble and insoluble matrix components and stromal cells. Here we report that in melanoma, turn-over of type I collagen (Col(I)), the predominant matrix protein in dermal stroma affects melanoma progression. Fibroblasts juxtaposed to melanoma cell nests within the papillary dermis display high levels of Col(I) mRNA expression. These nests are enveloped by collagen fibers. In contrast, melanoma-associated fibroblasts within the reticular dermis express Col(I) mRNA at a level that is comparable to its expression in uninvolved dermis and reduced amount of collagen protein can be observed. To determine the significance of Col(I) expression in melanoma, we pharmacologically inhibited its transcription in a porcine cutaneous melanoma model by oral administration of halofuginone. When administered before melanoma development, it reduced melanoma incidence and diminished the transition from microinvasive toward deeply invasive growth by limiting the development of a tumor vasculature. Whereas invasive melanoma growth has been correlated with increased blood vessel density previously, our data for the first time demonstrate that the proangiogenic effect of Col(I) expression by fibroblasts and vascular cells precedes the development of invasive melanomas in a de novo tumor model. ' 2007 Wiley-Liss, Inc.Key words: cutaneous melanoma; type I collagen; angiogenesis; MeLiM porcine melanoma model; halofuginone Tumor development and invasion into adjacent tissue is often accompanied by increased architectural disorder of the extracellular matrix (ECM) and cellular components especially at the invasive front of the neoplastic mass. 1 Along with increased production of extracellular proteolytic enzymes, 2-4 increased synthesis of type I collagen (Col(I)) and other matrix components by stromal cells has been documented in skin, mammary, colon and prostate carcinomas. [5][6][7][8][9] In squamous cell carcinomas of the skin, increased Col(I) synthesis by stromal fibroblasts 9 is also accompanied by enhanced remodeling due to increased activity of matrix proteinases. 10 In contrast, cutaneous melanoma, but with the exception of desmoplastic variants, is not associated with strong ECM remodeling, but is mainly characterized by pericellular proteolysis of Col(I) and elastin at the invasive front. 11 Expression of Col(I) and its contribution to melanoma development and progression have not been studied extensively.In skin, the fibril forming Col(I) is predominantly synthesized by fibroblasts and accounts for 80-90% of the collagenous proteins present in the dermis. 12 Col(I) fibers are composed of righthanded triple helical molecules of 1 Col(I)a2 and 2 Col(I)a1 chains and can be found in all dermal layers. 13 However, the architectural organization of Col(I) fibers is different in the papillary and reticular dermis. Whereas, Col(I) is found as a finely woven meshwork of fibers in the papillary dermis, a distinctive pattern of thick Col(I) bundles is found in reticular dermis.Th...

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Section: Halofuginone Affects Proliferation Of Pericytes In Vitrosupporting

confidence: 93%

Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

Kempen

Rijntjes

Mamor-Cornelissen

et al. 2007

Intl Journal of Cancer

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“…IFNγ for example, has also been shown to inhibit collagen synthesis and reduce ABCA1-mediated cholesterol efflux, and both IFNγ and TNFα can increase the expression of several MMPs that could potentially lead to plaque destabilization [61][62][63]. Reduced CD36 expression may not be athero-protective -while macrophages from CD36 deficient humans do show reduced oxLDL binding, patients are also more likely to exhibit hypertriglyceridemia, impaired glucose metabolism, and have mild hypertension 10 .…”

Section: Discussionmentioning

confidence: 99%

Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

Chu¹,

Tai²,

Beer³

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL). Classically-activated macrophages treated simultaneously with interferon γ (IFNγ) and tumour necrosis factor α (TNFα) associated with less oxLDL and accumulated less cholesterol compared to untreated controls. The combined treatment of IFNγ and TNFα reduced the mRNA expression of CD36 and the expression of both cell surface CD36 and macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions, IFNγ and TNFα did not reduce macrophage protein expression of the transcription factor peroxisome proliferator-actived receptor γ (PPARγ) which is known to positively regulate CD36 expression. However, macrophages treated with IFNγ did prevent the PPARγ-specific agonist rosiglitazone from upregulating cell surface CD36 protein expression. Our results demonstrate that the observed reduction of cholesterol accumulation in macrophages treated with IFNγ and TNFα following oxLDL treatment was due at least in part to reduced cell surface CD36 and MSR1 protein expression.

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“…Cell-culture studies have shown it to be a powerful growth inhibitor for endothelial cells and smooth muscle cells (SMCs) (16,17). In vivo studies in rats have shown that the proliferative response of SMCs after arterial injury is inhibited by IFN-g (18), which also inhibits smooth muscle contractility and collagen synthesis (17,19). It was therefore proposed that IFN-g-producing T cells could play an important role in plaque destabilization by reducing the fibrous cap (20).…”

Section: Discussionmentioning

confidence: 99%

Increased T-helper interferon-γ-secreting cells in obese children

Pacifico

Renzo²,

Anania³

et al. 2006

eur j endocrinol

165

115

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Objective: Leptin, an adipocyte-secreted hormone, has emerged as a potential candidate for the link between obesity and the proinflammatory state. Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with the secretion of proinflammatory cytokines. The aim of this study was to evaluate the Th1/Th2 balance in obese children and its relation with hormonal and metabolic features. Study design: In 50 obese children and 20 control children, we measured the CD4-positive Th cells that secrete interferon (IFN)-g or interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases, leptin and ghrelin. Obese children also underwent dual energy X-ray absorptiometry scan measurements, and liver ultrasound scanning. Results: Geometric mean percentages of IL-2-and IL-4-CD4 secreting cells in obese children were not significantly different from those found in control children. However, the geometric mean percentage of CD4-positive T cells secreting IFN-g was significantly higher in the obese than in the control (P , 0.0001, t-test) group. Within the entire group of study children, the percentage of IFN-g-positive cells was positively associated with leptin (P ¼ 0.002), insulin (P , 0.00 005), and HOMA-IR values (P , 0.00 005). However, when these associations were restricted to the group of obese subjects, insulin and HOMA-IR values, but not leptin, retained statistical significance. Yet, in the obese group, the percentage of IFN-g-positive cells was associated with nonalcoholic steatohepatitis (NASH) (P ¼ 0.001), but not with body mass index-standard deviation score and total body fat mass. Conclusions: In obese children, a shift to Th1-cytokine profile dominated by the production of IFN-g is related to insulin resistance as well as to NASH independently of anthropometric features and other metabolic characteristics. The prevalent Th1 pattern of secreted cytokines may be regarded as a mechanism contributing to inflammation in obesity.European Journal of Endocrinology 154 691-697

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Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells.

Cited by 525 publications

References 49 publications

Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

Increased T-helper interferon-γ-secreting cells in obese children

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