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@inproceedings{Derry:2018:10.1136/thorax-2018-212555.69,
author = {Derry, J and Patel, BV and Adcock, IM and Mumby, S},
doi = {10.1136/thorax-2018-212555.69},
pages = {A39--A39},
publisher = {BMJ PUBLISHING GROUP},
title = {Comparison of mechanisms of repair and regeneration in experimental models of acute respiratory distress syndrome},
url = {http://dx.doi.org/10.1136/thorax-2018-212555.69},
year = {2018}
}

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TY  - CPAPER
AB  - Background The acute respiratory distress syndrome (ARDS) is a clinical condition with multiple aetiologies. Previous work has presented two relevant, distinct animal models of ARDS. A murine model of aspiration using acid, in which the lung injury begins to resolve after 48 hours, and another of infection using LPS, that continues to deteriorate. It has been suggested that alveolar epithelial regeneration is implicated in disease progression to different extents between the models.We hypothesised that the wnt and retinoic acid pathways are involved in regeneration and resolution of these murine models of ARDS, and that there is greater activation of these pathways in the aspiration compared to the infection model. Currently, management of ARDS is irrespective of lung injury aetiology, and these mechanisms may prove relevant for pathway modulation for future therapy.Methods Mice were administered either 25 µl intratracheal 0.1 M hydrochloric acid (aspiration model, n=5), 25 µg LPS (infection model, n=6) or sham treated (controls, n=6) and sacrificed at 48 hours. Lung tissue was homogenised. mRNA and protein levels of regenerative pathway genes were quantified, through reverse-transcription polymerase chain reaction and Western blotting.Results Significant upregulation of all 9 regenerative genes studied was seen in the acid model compared to controls. Rac-2 mRNA (wnt pathways) was the only regenerative gene in the LPS-injured mice to show a significant upregulation compared to controls (67.39±25.73 vs 0.32±0.13 ΔCTx1010p<0.05). Significant differences between the acid and LPS models were seen in the mRNA levels of Daam-2 (wnt pathways, figure 1) and Retinol Binding Protein-1 (RBP-1) from the retinoic acid pathway (26.130±2.812 vs 4.893±0.564 ΔCTx105, p<0.05). There were inter-model differences in protein levels, most apparent in β-catenin (β-catenin dependen
AU  - Derry,J
AU  - Patel,BV
AU  - Adcock,IM
AU  - Mumby,S
DO  - 10.1136/thorax-2018-212555.69
EP  - 39
PB  - BMJ PUBLISHING GROUP
PY  - 2018///
SN  - 0040-6376
SP  - 39
TI  - Comparison of mechanisms of repair and regeneration in experimental models of acute respiratory distress syndrome
UR  - http://dx.doi.org/10.1136/thorax-2018-212555.69
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000471187500065&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://thorax.bmj.com/content/73/Suppl_4/A39.1
UR  - http://hdl.handle.net/10044/1/80753
ER  -

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