Repozitorij Univerze v Novi Gorici

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Naslov:Analysis of mechanosensing in human cardiac stem cells
Avtorji:ID Mazzega, Elisa, Department of Medical and Biological Sciences, University of Udine, Italy (Avtor)
ID Pomarè, Eliana, Department of Medical and Biological Sciences, University of Udine, Italy (Avtor)
ID Caragnano, Angela, Department of Medical and Biological Sciences, University of Udine, Italy (Avtor)
ID Martewicz, Sebastian, University of Padua, Padua, Italy (Avtor)
ID Elvassore, Nicola, University of Padua, Padua, Italy (Avtor)
ID Beltrami, Antonio Paolo, Department of Medical and Biological Sciences, University of Udine, Italy (Avtor)
ID Livi, Ugo, University Hospital Santa Maria della Misericordia, Udine, Italy (Avtor)
Datoteke: Gradivo nima datotek, ki so prostodostopne za javnost. Gradivo je morda fizično dosegljivo v knjižnici fakultete, zalogo lahko preverite v COBISS-u. Povezava se odpre v novem oknu
Jezik:Angleški jezik
Vrsta gradiva:Delo ni kategorizirano
Tipologija:1.12 - Objavljeni povzetek znanstvenega prispevka na konferenci
Organizacija:UNG - Univerza v Novi Gorici
Opis:Objectives: We have shown that age and pathology impair the biological properties of stem cells isolated from human hearts (CSC) and functional assays showed differences between CSC isolated from normal (DCSC) and end-stage failing (ECSC) hearts. As alterations of mechanical properties of the myocardium, such as stiffening and increased wall stress, are crucial features of cardiac remodeling, this work addresses the biological effects exerted on CSC by mechanical stimuli. Materials and methods: DCSC and ECSC were cultured under defined conditions to mimic specific features of the pathologic condition: increased mechanical loading (up to 15%, cyclic at 1 Hz), differential substrate stiffness (ranging from 1 to 231 kPa), differential cell densities. After 24, 48 and 72 h, cells were fixed and stained for analysis of proliferation and subcellular localization of YAP or lysed for RT-PCR analysis.Results: Cyclic stretch was significantly associated with both increased proliferation of DCSC (n = 6, p<0.0001) and ECSC (n = 4, p = 0.003), and with a significant reduction of nuclear localized YAP (nYAP) as a function of time (p<0.05). However, while significant correlation between cell density and decreased nYAP (p = 0.003, r2 = 0.37) characterized ECSC, this was not evident for unstretched DCSC, suggesting a less stringent regulation of contact inhibition in DCSC. These data were further confirmed by seeding cells at differential density. As opposed to what previously shown for epithelial cell lines, DCSC did not reduce nYAP positivity as a function of cell density, when grown in serum containing medium, suggesting that soluble factors present in the serum could maintain the nuclear localization of YAP, independently from the cell density. In line, serum significantly increased the nYAP expressing cells in DCSC, while a significant positive correlation between cell density and nYAP positivity can be demonstrated in DCSC cultured in serum free medium. RT-PCR for YAP-regulated targets confirmed immuno- fluorescence data. Furthermore, independently from the pathologic status, cyclic stretch was significantly associated with a persistent YAP signaling at high cell density. Besides, tension and assembly of cytoskeletal network, induced by increasing substrate stiffness, correlates with nYAP (p<0.05) and YAP transcriptional activation (p<0.05). Conclusions: D- and ECSC differ in their mechanosensing properties. However, in the first cell type, nYAP localization is dictated by the combined action of paracrine factors and cytoskeletal tension, thus reducing the contact inhibition effect. This finding is in line with a more primitive phenotype of SC isolated from normal hearts.
Ključne besede:Stem cells, human cardiac stem cells, mechanosensing, mechanotransduction, heart failure, YAP
Leto izida:2015
PID:20.500.12556/RUNG-3028-a6bfcf8c-d679-120d-7f34-f743071bb726 Novo okno
COBISS.SI-ID:4724987 Novo okno
DOI:10.1016/j.vph.2015.11.050 Novo okno
NUK URN:URN:SI:UNG:REP:GBV0W0KR
Datum objave v RUNG:21.03.2017
Število ogledov:4250
Število prenosov:0
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
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Gradivo je del monografije

Naslov:Vascular Pharmacology
Kraj izida:Vascular Pharmacology
Leto izida:2015
Prireditelj konference:SIRC

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