University of Groningen
Novel therapeutic targets for the treatment of asthma
van den Berg, M.P.M.
DOI:
10.33612/diss.143959597
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2020
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
van den Berg, M. P. M. (2020). Novel therapeutic targets for the treatment of asthma: Focus on Arginase and TRPA1. University of Groningen. https://doi.org/10.33612/diss.143959597
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg Processed on: 14-10-2020 Processed on: 14-10-2020 Processed on: 14-10-2020
Processed on: 14-10-2020 PDF page: 1PDF page: 1PDF page: 1PDF page: 1
Novel Therapeutic Targets for the
Treatment of Asthma
Focus on Arginase and TRPA1
548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg Processed on: 14-10-2020 Processed on: 14-10-2020 Processed on: 14-10-2020
Processed on: 14-10-2020 PDF page: 2PDF page: 2PDF page: 2PDF page: 2 The studies described in this thesis were performed within the framework of the
Groningen University Institute for Drug Exploration (GUIDE), the Groningen Research Institute for Pharmacy (GRIP) and the Groningen Research Institute for Asthma and COPD (GRIAC), and is part of the research programme ‘Connecting Innovators’ with project number 13547 which is (partly) financed by the Netherlands Organisation for Scientific Research (NWO).
Printing of this thesis was financially supported by University of Groningen (RuG)
Graduate School of Science and Engineering (GSSE) Boehringer Ingelheim bv
Paranymphs Sophie Bos Xinhui Wu
Colofon
Copyright© 2020 by Mariska P.M. van den Berg
All rights reserved. No part of this book may be reproduced or transmitted in any form, or by any means, electronic, by print, or otherwise, without permission in writing from the author, or when appropriate, from the publishers of the respective publications. Thesis Cover: Sophie Bos
Layout and design: Stijn Eikenaar, persoonlijkproefschrift.nl Printing: Gildeprint Enschede, gildeprint.nl
548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg Processed on: 14-10-2020 Processed on: 14-10-2020 Processed on: 14-10-2020
Processed on: 14-10-2020 PDF page: 3PDF page: 3PDF page: 3PDF page: 3
Novel Therapeutic Targets for the
Treatment of Asthma
Focus on Arginase and TRPA1
Proefschrift
ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. C. Wijmenga en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op vrijdag 13 november om 14.30 uur
door
Mariska Petronella Maria van den Berg
geboren op 9 augustus 1992 te Boxmeer
548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg Processed on: 14-10-2020 Processed on: 14-10-2020 Processed on: 14-10-2020
Processed on: 14-10-2020 PDF page: 4PDF page: 4PDF page: 4PDF page: 4
Promotores
Prof. dr. R. Gosens Prof. dr. H. MeursBeoordelingscommissie
Prof. dr. J.K. Burgess
Prof. dr. G. Folkerts
Prof. dr. G. Caramori
548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg Processed on: 14-10-2020 Processed on: 14-10-2020 Processed on: 14-10-2020
Processed on: 14-10-2020 PDF page: 5PDF page: 5PDF page: 5PDF page: 5 Smile, breathe and go slowly
548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg Processed on: 14-10-2020 Processed on: 14-10-2020 Processed on: 14-10-2020
548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg 548933-L-sub01-bw-vdBerg Processed on: 14-10-2020 Processed on: 14-10-2020 Processed on: 14-10-2020
Processed on: 14-10-2020 PDF page: 7PDF page: 7PDF page: 7PDF page: 7
Contents
Chapter 1 General Introduction 8
Chapter 2 Pharmacological screening identifies SHK242 and SHK277 as novel
arginase inhibitors with efficacy against allergen-induced airway narrowing in vitro and in vivo
36
Chapter 3 Targeting arginase and nitric oxide metabolism in chronic airway
diseases and their co-morbidities 62
Chapter 4 Arginase 2 regulates mast cell proliferation and differentiation via
ornithine metabolism 76
Chapter 5 The novel TRPA1 antagonist BI01305834 inhibits
ovalbumin-induced bronchoconstriction in guinea pigs 98
Chapter 6 General Discussion 124 Dutch Summary / Nederlandse Samenvatting 142
Acknowledgements / Dankwoord 154
Curriculum vitae 166
