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Saliba Y.,Saint - Joseph University | Karam R.,Saint - Joseph University | Smayra V.,Saint - Joseph University | Aftimos G.,National Institute of Pathology | And 3 more authors.
Journal of the American Society of Nephrology | Year: 2015

Transient receptor potential canonical (TRPC) Ca2+-permeant channels, especially TRPC3, are increasingly implicated in cardiorenal diseases. We studied the possible role of fibroblast TRPC3 in the development of renal fibrosis. In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolated cultured rat renal fibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3 was sufficient to inhibit both angiotensin II-and 1-oleoyl-2-acetyl-sn-glycerolinduced Ca2+ entry in these cells, which was detected by fura-2 Ca2+ imaging. TRPC3 blockade or Ca2+ removal inhibited fibroblast proliferation andmyofibroblast differentiation by suppressing the phosphorylation of extracellular signalregulated kinase (ERK1/2). In addition, pyr3 inhibited fibrosis and inflammation-associated markers in a noncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologic findings. In adult Male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 expression increased in the fibroblasts of obstructed kidneys and was associated with increased Ca2+ entry, ERK1/2 phosphorylation, and fibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout in mice inhibited ERK1/2 phosphorylation and fibroblast activation as well as myofibroblast differentiation and extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damage and renal fibrosis. In conclusion, TRPC3 channels are present in renal fibroblasts and control fibroblast proliferation, differentiation, and activation through Ca2+-mediated ERK signaling. TRPC3 channelsmight constitute important therapeutic targets for improving renal remodeling in kidney disease. © 2015 by the American Society of Nephrology.

Fares N.,St Joseph University | Nader L.,St Joseph University | Saliba Y.,St Joseph University | Aftimos G.,National Institute of Pathology | Gebara V.,Laboratory of Physiology
Journal Medical Libanais | Year: 2010

Natriuretic peptides seem to be a potent regulator of cell Ca 2+ signalling in their action on the cardiovascular system. It was therefore the aim of this study to investigate the effect(s) of B-type natriuretic peptide (BNP) on the action potential and the L-type calcium current (I CaL) in the rat left ventricular myocytes. Perforated and whole cell patch clamp technique was used to record action potential (AP) and ICaL in current and voltage clamp mode, respectively. At the concentration tested of 10 -7 M, BNP significantly increased the action potential duration at 50% and at 90% of repolarization by 16.85% and 16.39% respectively, and the phase II slope of the AP by 52.5% ; reduced the I CaL amplitude with a 16.17% decrease in the peak amplitude ; reduced (16.51%) the inactivation time course of current decay; increased the V 0.5activation of the L-type calcium channel by 32.84% and decreased V 0.5 inactivation by 34.39%. These data suggest that BNP modulates cardiomyocyte function by reducing I CaL and modifying the AP. This study may show a novel facet to evaluate the paracrine/autocrine effect of BNP on the normal heart function.

Chen X.,Fudan University | Zheng Y.,Shanghai JiaoTong University | Manole C.G.,University of Bucharest | Manole C.G.,National Institute of Pathology | And 2 more authors.
Journal of Cellular and Molecular Medicine | Year: 2013

Telocytes (TCs), a new type of interstitial cells, were identified in many different organs and tissues of mammalians and humans. In this study, we show the presence, in human oesophagus, of cells having the typical features of TCs in lamina propria of the mucosa, as well as in muscular layers. We used transmission electron microscopy (TEM), immunohistochemistry (IHC) and primary cell culture. Human oesophageal TCs present a small cell body with 2-3 very long Telopodes (Tps). Tps consist of an alternation of thin segments (podomers) and thick segments (podoms) and have a labyrinthine spatial arrangement. Tps establish close contacts ('stromal synapses') with other neighbouring cells (e.g. lymphocytes, macrophages). The ELISA testing of the supernatant of primary culture of TCs indicated that the concentrations of VEGF and EGF increased progressively. In conclusion, our study shows the existence of typical TCs at the level of oesophagus (mucosa, submucosa and muscular layer) and suggests their possible role in tissue repair. © 2013 The Authors.

Nader L.,Saint - Joseph University | Lahoud L.,National Institute of Pathology | Chouery E.,Saint - Joseph University | Aftimos G.,Saint - Joseph University | And 2 more authors.
Annales de Cardiologie et d'Angeiologie | Year: 2010

Brain natriuretic peptide (BNP) binds to three types of natriuretic peptide receptors, NPR-A, -B and -C (NPRs). The expression shape of BNP and NPRs seems to be an important modulator factor in the pathogenesis of cardiac hypertrophy. The aim of this study was to evaluate the expression of NPRs in an animal model of pressure overload hypertrophy. Left ventricular hypertrophy was induced by chronic abdominal aortic banding in adult male Wistar rats. After six weeks, NPRs gene expression was evaluated with RT-PCR, BNP plasma concentration and BNP positive myocytes were measured with ELISA and immunohistochemistry techniques respectively. NPR-A and NPR-C mRNA expression was significantly increased in left ventricular hypertrophied cardiomyocytes by 1.6-fold and 2.1-fold respectively (P<0.01). Abdominal aortic banding increased significantly BNP plasma concentration (630 ± 8 pg/ml vs 106 ± 4 pg/ml; P< 0.01). The percentage of BNP positive cells in normal myocardial tissue were 40% while in the hypertrophied one it raised to 80%. The data suggest that in our left ventricular hypertrophy model, the NPR-A and NPR-C receptors were increased in association to the increased BNP level. This relationship may amplify beneficial paracrine/autocrine effects of BNP on cardiac remodelling in response to hemodynamic overload. © 2009 Elsevier Masson SAS.

Raducanu A.,National Institute for Energy Research and Development ICEMENERG | Codorean E.,National Institute of Pathology | Grigoriu C.,Institute for Laser | Meghea A.,Polytechnic University of Bucharest
UPB Scientific Bulletin, Series B: Chemistry and Materials Science | Year: 2011

Workplace dusts generated in power plants, with particular reference to thermal power of Mintia - Deva have been studied. In order to determine the chemical composition of powder structural analysis was used by corroborating data obtained by elemental analysis performed by two methods: atomic absorption spectrometry and SEM-EDAX. Dust collected from various locations in power plant contained more than 25% SiO 2, 4% Al2O3 10% Fe2O3. The impact of these particles on health workers in these different workplaces was assessed by specific biochemical and hematological tests. The level of cytokines was proposed as an indicator for the inflammatory processes associated with exposure to occupational hazards.

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