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- W2770669208 abstract "TGFs is a widely distributed, pleiotropic cytokine implicated in tissue remodelling in many diseases including severe asthma. It is secreted in a latent form that requires activation for function. Mechanotransduction of intracellular forces through cell surface integrins can lead to TGFs activation. We have previously shown that human airway smooth muscle (HASM) cells can activate TGFβ via αvβ5 integrins. In the present study we have investigated the effect of extracellular matrix (ECM) on basal TGFβ activation in primary asthmatic and non-asthmatic HASM cells. We assessed basal TGFβ activation in non-asthmatic (n=9) and asthmatic (n=7) HASM cells. TGFβ activation was assessed using a TGFβ reporter cell assay and a phosphorylated Smad2 ELISA. Cell contractility was assessed using a collagen gel contraction assay and traction force microscopy. ECM was isolated from HASM cells and cross-over experiments performed where non-asthmatic cells were cultured on asthmatic ECM and vice-versa then TGFβ activity determined. Expression of ECM crosslinking enzymes was determined at the mRNA and protein levels. Finally, expression of LOXL2 was determined in an Aspergillus fumigatus model of asthma.Asthmatic HASM cells activated 3-fold higher levels of TGFβ basally than non-asthmatic cells (p LOXL2 and LOXL3 was significantly increased in asthmatic HASMs (p Asp. f compared with control challenged animals. In conclusion HASM cells derived from asthmatic patients exhibit enhanced activation of TGFβ compared with non-asthmatic HASM cells. This may be driven by the diseased ECM since asthmatic HASMs cells exhibit aberrant expression of ECM crosslinking enzymes." @default.
- W2770669208 created "2017-12-04" @default.
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- W2770669208 date "2017-11-15" @default.
- W2770669208 modified "2023-09-23" @default.
- W2770669208 title "S86 Extracellular matrix deposited by asthmatic human airway smooth muscle cells enhances basal activation of tgfβ" @default.
- W2770669208 doi "https://doi.org/10.1136/thoraxjnl-2017-210983.92" @default.
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