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Ping Kong Panagiota Christia Nikolaos G. Frangogiannis 《Cellular and molecular life sciences : CMLS》2014,71(4):549-574
Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. This review discusses the cellular effectors and molecular pathways implicated in the pathogenesis of cardiac fibrosis. Although activated myofibroblasts are the main effector cells in the fibrotic heart, monocytes/macrophages, lymphocytes, mast cells, vascular cells and cardiomyocytes may also contribute to the fibrotic response by secreting key fibrogenic mediators. Inflammatory cytokines and chemokines, reactive oxygen species, mast cell-derived proteases, endothelin-1, the renin/angiotensin/aldosterone system, matricellular proteins, and growth factors (such as TGF-β and PDGF) are some of the best-studied mediators implicated in cardiac fibrosis. Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible. Understanding the mechanisms responsible for initiation, progression, and resolution of cardiac fibrosis is crucial to design anti-fibrotic treatment strategies for patients with heart disease. 相似文献
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Omar K. Matar Panagiota Angeli Geoffrey F. Hewitt E. Susana Pérez de Ortiz 《清华大学学报》2006,11(2):202-206
Introduction Liquid-liquid dispersions in agitated vessels are fre-quently used in the chemical industry for conducting operations such as solvent extraction and heterogene-ous reactions. In liquid-liquid two-phase flow systems, usually consisting of an a… 相似文献
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A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours 总被引:1,自引:0,他引:1
Beck B Driessens G Goossens S Youssef KK Kuchnio A Caauwe A Sotiropoulou PA Loges S Lapouge G Candi A Mascre G Drogat B Dekoninck S Haigh JJ Carmeliet P Blanpain C 《Nature》2011,478(7369):399-403
Angiogenesis is critical during tumour initiation and malignant progression. Different strategies aimed at blocking vascular endothelial growth factor (VEGF) and its receptors have been developed to inhibit angiogenesis in cancer patients. It has become increasingly clear that in addition to its effect on angiogenesis, other mechanisms including a direct effect of VEGF on tumour cells may account for the efficiency of VEGF-blockade therapies. Cancer stem cells (CSCs) have been described in various cancers including squamous tumours of the skin. Here we use a mouse model of skin tumours to investigate the impact of the vascular niche and VEGF signalling on controlling the stemness (the ability to self renew and differentiate) of squamous skin tumours during the early stages of tumour progression. We show that CSCs of skin papillomas are localized in a perivascular niche, in the immediate vicinity of endothelial cells. Furthermore, blocking VEGFR2 caused tumour regression not only by decreasing the microvascular density, but also by reducing CSC pool size and impairing CSC renewal properties. Conditional deletion of Vegfa in tumour epithelial cells caused tumours to regress, whereas VEGF overexpression by tumour epithelial cells accelerated tumour growth. In addition to its well-known effect on angiogenesis, VEGF affected skin tumour growth by promoting cancer stemness and symmetric CSC division, leading to CSC expansion. Moreover, deletion of neuropilin-1 (Nrp1), a VEGF co-receptor expressed in cutaneous CSCs, blocked VEGF's ability to promote cancer stemness and renewal. Our results identify a dual role for tumour-cell-derived VEGF in promoting cancer stemness: by stimulating angiogenesis in a paracrine manner, VEGF creates a perivascular niche for CSCs, and by directly affecting CSCs through Nrp1 in an autocrine loop, VEGF stimulates cancer stemness and renewal. Finally, deletion of Nrp1 in normal epidermis prevents skin tumour initiation. These results may have important implications for the prevention and treatment of skin cancers. 相似文献
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Foreman J Demidchik V Bothwell JH Mylona P Miedema H Torres MA Linstead P Costa S Brownlee C Jones JD Davies JM Dolan L 《Nature》2003,422(6930):442-446
Cell expansion is a central process in plant morphogenesis, and the elongation of roots and root hairs is essential for uptake of minerals and water from the soil. Ca2+ influx from the extracellular store is required for (and sets the rates of) cell elongation in roots. Arabidopsis thaliana rhd2 mutants are defective in Ca2+ uptake and consequently cell expansion is compromised--rhd2 mutants have short root hairs and stunted roots. To determine the regulation of Ca2+ acquisition in growing root cells we show here that RHD2 is an NADPH oxidase, a protein that transfers electrons from NADPH to an electron acceptor leading to the formation of reactive oxygen species (ROS). We show that ROS accumulate in growing wild-type (WT) root hairs but their levels are markedly decreased in rhd2 mutants. Blocking the activity of the NADPH oxidase with diphenylene iodonium (DPI) inhibits ROS formation and phenocopies Rhd2-. Treatment of rhd2 roots with ROS partly suppresses the mutant phenotype and stimulates the activity of plasma membrane hyperpolarization-activated Ca2+ channels, the predominant root Ca2+ acquisition system. This indicates that NADPH oxidases control development by making ROS that regulate plant cell expansion through the activation of Ca2+ channels. 相似文献
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G Mascré S Dekoninck B Drogat KK Youssef S Broheé PA Sotiropoulou BD Simons C Blanpain 《Nature》2012,489(7415):257-262
The skin interfollicular epidermis (IFE) is the first barrier against the external environment and its maintenance is critical for survival. Two seemingly opposite theories have been proposed to explain IFE homeostasis. One posits that IFE is maintained by long-lived slow-cycling stem cells that give rise to transit-amplifying cell progeny, whereas the other suggests that homeostasis is achieved by a single committed progenitor population that balances stochastic fate. Here we probe the cellular heterogeneity within the IFE using two different inducible Cre recombinase–oestrogen receptor constructs targeting IFE progenitors in mice. Quantitative analysis of clonal fate data and proliferation dynamics demonstrate the existence of two distinct proliferative cell compartments arranged in a hierarchy involving slow-cycling stem cells and committed progenitor cells. After wounding, only stem cells contribute substantially to the repair and long-term regeneration of the tissue, whereas committed progenitor cells make a limited contribution. 相似文献
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Konstantina Katsarou Alexandros Α. Lavdas Panagiota Tsitoura Elisavet Serti Panagiotis Markoulatos Penelope Mavromara Urania Georgopoulou 《Cellular and molecular life sciences : CMLS》2010,67(14):2491-2506
Although HCV is an enveloped virus, naked nucleocapsids have been reported in the serum of infected patients. The HCV core
particle serves as a protective capsid shell for the viral genome and recombinant in vitro assembled HCV core particles induce
strong specific immunity. We investigated the post-binding mechanism of recombinant core particle uptake and its intracellular
fate. In hepatic cells, these particles are internalized, most likely in a clathrin-dependent pathway, reaching early to late
endosomes and finally lysosomes. The endocytic acidic milieu is implicated in trafficking process. Using specific phosphoantibodies,
signaling pathway inhibitors and chemical agents, ERK1/2 was found to be activated in a sustained way after endocytosis, followed by downstream immediate early genes (c-fos and egr-1) modulation. We propose that the intriguing properties of cellular internalization of HCV non-enveloped particles can induce
specific ERK1/2–MAPKs events that could be important in HCV life cycle and pathogenesis of HCV infection. 相似文献
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