Search results for "fibroblast"
showing 10 items of 667 documents
Reduction of Cardiac Fibrosis by Interference With YAP-Dependent Transactivation
2022
Background: Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interf…
Interactions between cholinergic and fibroblast growth factor receptors in brain trophism and plasticity
2014
Acetylcholine, acting on both nicotinic receptors (nAChRs) and muscarinic receptors (mAChRs), plays a role in the regulation of synaptic plasticity, being involved in the regulation of cellular processes and cognitive functions, such as learning, memory and attention. Recently, G protein coupled receptors (GPCRs), including mAChRs, have been reported to transactivate tyrosine-kinase receptors (RTK), such as epidermal growth factor receptor (EGFR), and initiate their intracellular signaling. In this minireview we have first analysed the RTK transactivation mechanisms, involving cholinergic receptors, and thereafter the interplay between AChR and neurotrophic factor systems built up by FGF2 a…
Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis.
1999
Neutrophil-borne heparin-binding protein (HBP) is a multifunctional protein involved in the progression of inflammation. HBP is stored in neutrophil granules and released upon stimulation of the cells in proximity to endothelial cells. HBP affects endothelial cells in multiple ways; however, the molecular and cellular mechanisms underlying the interaction of HBP with these cells are unknown. Affinity isolation and enzymatic degradation demonstrated that HBP released from human neutrophils binds to endothelial cell-surface proteoglycans, such as syndecans and glypican. Flow cytometry indicated that a significant fraction of proteoglycan-bound HBP is taken up by the endothelial cells, and we …
Analysis of the Biological Response of Endothelial and Fibroblast Cells Cultured on Synthetic Scaffolds with Various Hydrophilic/Hydrophobic Ratios: …
2009
In this study we developed polymer scaffolds intended as anchorage rings for cornea prostheses among other applications, and examined their cell compatibility. In particular, a series of interconnected porous polymer scaffolds with pore sizes from 80 to 110 microns were manufactured varying the ratio of hydrophobic to hydrophilic monomeric units along the polymer chains. Further, the effects of fibronectin precoating, a physiological adhesion molecule, were tested. The interactions between the normal human fibroblast cell line MRC-5 and primary human umbilical vein endothelial cells (HUVECs) with the scaffold surfaces were evaluated. Adhesion and growth of the cells was examined by confocal…
Improving mRNA-Based Therapeutic Gene Delivery by Expression-Augmenting 3' UTRs Identified by Cellular Library Screening.
2019
Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3′ UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3′ UTRs that augment the expression of proteins encoded by synthetic mRNA. Moreover, we show, for two applications of mRNA therapeutics, namely, (1) …
The 3'-UTR of the mRNA coding for the major protein kinase C substrate MARCKS contains a novel CU-rich element interacting with the mRNA stabilizing …
2003
The expression of the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) is controlled by the stability of its mRNA. While the MARCKS mRNA is long living in quiescent fibroblasts (t1/2 = 14 h), its half-life time is drastically reduced (t1/2 = 2 h) in cells treated with phorbol esters to activate protein kinase C (PKC) or treated with growth factors. In a first step to study the underlying mechanism we identified both a cis-element on the MARCKS mRNA and the corresponding trans-acting factors. Fusing the complete 3'-UTR or specific regions of the 3'-UTR of the MARCKS gene to a luciferase reporter gene caused a drastic decrease in luciferase expression to…
Liver specific overexpression of platelet-derived growth factor-B accelerates liver cancer development in chemically induced liver carcinogenesis
2010
A genetic basis of hepatocellular carcinoma (HCC) has been well-established and major signaling pathways, such as p53, Wnt-signaling, transforming growth factor-β (TGF-β) and Ras pathways, have been identified to be essential to HCC development. Lately, the family of platelet-derived growth factors (PDGFs) has shifted to the center of interest. We have reported on spontaneously developing liver fibrosis in PDGF-B transgenic mice. Since HCC rarely occurs in healthy liver, but dramatically increases at the cirrhosis stage of which liver fibrosis is a preliminary stage, we investigated liver cancer development in chemically induced liver carcinogenesis in these mice. HCC induction was performe…
Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascul…
2012
Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), …
ASTROCYTES SHED EXTRACELLULAR VESICLES THAT CONTAIN FIBROBLAST GROWTH FACTOR-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR.
2007
An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the perme…
NEURONS PRODUCE FGF-2 AND VEGF SECRETE THEM AT LEST IN PART BY SHEDDING EXTRACELLULAR VESCICLES
2007
Abstract We previously found that neurons are able to affect the ability of brain capillary endothelial cells to form in vitro a monolayer with properties resembling the blood-brain barrier. We then looked, by immunofluorescence and western analysis, for factors, produced by neurons, with the potential to influence growth and differentiation of endothelial cells. In the present paper, we report that neurons produce both vascular endothelial growth factor and fibroblast growth factor 2, two well-known angiogenic factors. More interestingly, we gained evidence that both factors are released by neurons, at least in part, by shedding of extracellular vesicles, that contain β1 integrin, a membra…