Search results for "Forming"
showing 10 items of 1719 documents
Colorectal cancer-derived small extracellular vesicles induce TGFβ1-mediated epithelial to mesenchymal transition of normal hepatocytes: new insights…
2023
More than 50% of patients affected by colorectal cancer (CRC) present liver metastasis, which is the most frequent cause of CRC-associated death. Numerous studies have shown that metastatic cascade is the result of complex mechanisms based on two-way interactions between invasive CRC cells and liver resident cells. In recent years, several findings have demonstrated that small extracellular vesicles (SEVs) released by cancer cells play a crucial role in the formation of pre-metastatic niche in the liver, specifically affecting the activities of non-parenchymal cells as Kupffer cells and hepatic stellate cells. However, although hepatocytes (heps) are the most conspicuous in the liver, their…
Induction of collagenase-3 (MMP-13) expression in human skin fibroblasts by three-dimensional collagen is mediated by p38 mitogen-activated protein k…
1999
Collagenase-3 (matrix metalloproteinase-13, MMP-13) is a recently identified human MMP with an exceptionally wide substrate specificity and restricted tissue-specific expression. Here we show that MMP-13 expression is induced in normal human skin fibroblasts cultured within three-dimensional collagen gel resulting in production and proteolytic activation of MMP-13. Induction of MMP-13 mRNAs by collagen gel was potently inhibited by blocking antibodies against alpha1 and alpha2 integrin subunits and augmented by activating antibody against beta1 integrin subunit, indicating that both alpha1 beta1 and alpha2 beta1 integrins mediate the MMP-13-inducing cellular signal generated by three-dimens…
The Late Endosomal Adaptor Molecule p14 (LAMTOR2) Regulates TGFβ1-Mediated Homeostasis of Langerhans Cells
2014
Langerhans cells (LCs), a sub-population of dendritic cells (DCs) in the skin, participate in the regulation of immunity and peripheral tolerance. The adaptor molecule p14 is part of the late endosomal/lysosomal adaptor and mitogen-activated protein kinase and mammalian target of rapamycin (mTOR) activator/regulator (LAMTOR) complex, which mediates the activation of lysosome-associated extracellular signaling regulated kinase (ERK) and the mTOR cascade. In previous work, we demonstrated that CD11c-specific deficiency of p14 disrupts LC homeostasis by affecting the LAMTOR-mediated ERK and mTOR signaling. In this study, we extended our analysis on p14 deficiency specifically in LCs. Langerin-…
Heat shock proteins in fibrosis and wound healing: Good or evil?
2014
Heat shock proteins (HSPs) are key regulators of cell homeostasis, and their cytoprotective role has been largely investigated in the last few decades. However, an increasing amount of evidence highlights their deleterious effects on several human pathologies, including cancer, in which they promote tumor cell survival, proliferation and drug resistance. Therefore, HSPs have recently been suggested as therapeutic targets for improving human disease outcomes. Fibrotic diseases and cancer share several properties; both pathologies are characterized by genetic alterations, uncontrolled cell proliferation, altered cell interactions and communication and tissue invasion. The discovery of new HSP…
Global Functional Analyses of Cellular Responses to Pore-Forming Toxins
2011
Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs). PFTs are uniquely important bacterial virulence factors, comprising the single largest class of bacterial protein toxins and being important for the pathogenesis in humans of many Gram positive and Gram negative bacteria. Their mode of action is deceptively simple, poking holes in the plasma membrane of cells. The scattered studies to date of PFT-host cell interactions indicate a handful of genes are involved in cellular defenses to PFTs. How many genes are involved in cellular defenses against PFTs and how cellular defenses are coordinated are unknown. To address these questions, we pe…
CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner.
2007
Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β−/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, redu…
Low-complexity AoA and AoD estimation in the transformed spatial domain for millimeter wave MIMO channels
2021
La estimación del ángulo de llegada (AoA) y del ángulo de salida (AoD) es fundamental para la búsqueda de celdas, las comunicaciones estables y el posicionamiento en los sistemas celulares de ondas milimétricas (mmWave). Además, el diseño de algoritmos de estimación de AoA/AoD de baja complejidad resulta también de gran importancia en el despliegue de sistemas prácticos para permitir un cálculo rápido y eficiente de la conformación de haz. La estimación paramétrica del canal en ondas milimétricas permite describir la matriz del canal como una combinación de trayectorias de señales dependientes de la dirección, explotando la característica de dispersión de los canales mmWave. En este context…
4-Dechloro-14-deoxy-oxacyclododecindione and 14-deoxy-oxacylododecindione, two inhibitors of inducible connective tissue growth factor expression fro…
2015
Connective tissue growth factor (CTGF/CCN2), a member of the CCN superfamily of secreted cysteine-rich glycoproteins, is a central mediator of tissue remodeling and fibrosis. CTGF is suggested to be an important down-stream effector of transforming growth factor-beta (TGF-β) signaling and has therefore reached considerable pathophysiological relevance because of its involvement in the pathogenesis of fibrotic diseases, atherosclerosis, skin scarring, and other conditions with excess production of connective tissue. In a search for inhibitors of inducible CTGF expression from fungi, two new macrocyclic lactones, namely 4-dechloro-14-deoxy-oxacyclododecindione (1) and 14-deoxy-oxacylododecind…
Keratinocyte-Derived Granulocyte-Macrophage Colony Stimulating Factor Accelerates Wound Healing: Stimulation of Keratinocyte Proliferation, Granulati…
2001
Chronic, nonhealing wounds represent a major clinical challenge to practically all disciplines in modern medicine including dermatology, oncology, surgery, and hematology. In skin wounds, granulocyte-macrophage colony stimulating factor (GM-CSF) is secreted by keratinocytes shortly after injury and mediates epidermal cell proliferation in an autocrine manner. Many other cells involved in wound healing including macrophages, lymphocytes, fibroblasts, endothelial cells, and dendritic cells synthesize GM-CSF and/or are targets of this cytokine. Therefore, GM-CSF is a pleiotropic cytokine evoking complex processes during wound repair. Despite this complexity and the scarcity of mechanistic unde…
Tumor necrosis factor (TNF)-alpha but not TNF-beta induces secretion of colony stimulating factor for macrophages (CSF-1) by human monocytes
1987
Abstract Tumor necrosis factor (TNF)-alpha has been identified as a major inducer of colony stimulating factor (CSF)-secretion by human vascular endothelial cells and fibroblasts. In the present study we assessed the capacity of TNFs to induce release of CSF-1 from highly purified peripheral blood monocyte preparations. Whereas monocytes do not accumulate CSF-1 messenger (m)RNA constitutively and consequently do not produce CSF-1 protein, CSF-1 mRNA and protein secretion became detectable, when monocytes were cultured in the presence of TNF-alpha, that was synergistically enhanced by interferon-gamma (IFN-gamma). However, under identical experimental conditions TNF-beta failed to induce mon…