1 Differential expression of soluble receptor for advanced glycation end-products (sRAGE) in 1 mice susceptible or resistant to chronic colitis 2 3 Michael Bramhall 1,2 , Kevin Rich 2 , Ajanta Chakraborty 2 , Larisa Logunova 2 , Namshik Han 3,4 , 4 James Wilson 5 , Catherine Booth 5 , John Mclaughlin 3,6 , Andy Brass 3 , Sheena M. Cruickshank 2 5 6 Author Affiliations: 7 1 Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash 8 University, Clayton, Victoria 3800, Australia 9 2 Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health 10 Science Centre, School of Biological Sciences, Faculty of Biology, Medicine, and 11 Health, University of Manchester, Manchester M13 9PT, UK 12 3 Manchester Academic Health Science Centre, School of Medical Sciences, The University of 13 Manchester, Manchester M13 9PT, UK 14 4 The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK 15 5 Epistem Ltd., Manchester M13 9XX, UK 16 6 Salford Royal NHS Foundation Trust, Salford M6 8HD UK 17 Running title: Markers of protective responses in colitis 18 19 Corresponding Author 20 S. M. Cruickshank, AV Hill Building, University of Manchester, Manchester M13 9PT, UK 21 [email protected], Phone +44 (0)161 275 1578 22 not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was this version posted August 5, 2019. ; https://doi.org/10.1101/719310 doi: bioRxiv preprint
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Differential expression of soluble receptor for …...2019/08/05 · 21 S. M. Cruickshank, AV Hill Building, University of Manchester, Manchester M13 9PT, UK 22 [email protected],
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onset of chronic colitis, and that further study of sRAGE in IBD may provide a novel42
diagnosticandtherapeutictarget.43
44
Keywords:sRAGE,colitis,mouse45
46
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not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which wasthis version posted August 5, 2019. ; https://doi.org/10.1101/719310doi: bioRxiv preprint
not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which wasthis version posted August 5, 2019. ; https://doi.org/10.1101/719310doi: bioRxiv preprint
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were carried out using GraphPad Prism 7 (GraphPad Software, La Jolla, California, USA;119
www.graphpad.com). 120
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not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which wasthis version posted August 5, 2019. ; https://doi.org/10.1101/719310doi: bioRxiv preprint
not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which wasthis version posted August 5, 2019. ; https://doi.org/10.1101/719310doi: bioRxiv preprint
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an indicator of whether sRAGE might be quenching the proinflammatory effects of214
circulating RAGE ligands by acting as a decoy receptor. Serum and faecal S100A8 did215
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picture,wherewehad a subset of patients undergoing routine test thatwere expressing239
bothsRAGEandCalprotectin. 240
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important to validate results from mouse model to human disease and therefore we261
conducted a small validation study to assess faecal sRAGE. Faecal sRAGE was readily262
detected in patient’s faecal samples. Akin to the mouse data we saw lower sRAGE in263
patients with active chronic inflammation. Surprisingly, symptomatic patients with IBD264
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process by which epithelial cells may undergo RAGE shedding represents an important288
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clinical practice as an IBD biomarker to aid clinical diagnosis non-invasively, but336
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The Bioimaging Facilitymicroscopes used in this study were purchasedwith grants from361
BBSRC,Wellcome and the University ofManchester Strategic Fund. Special thanks go to362
RogerMeadowsfrom the Bioimaging Facility for his helpwith themicroscopy and image363
acquisition. 364
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