University of Groningen
Biochemical and biomechanical regulation of the myofibroblast phenotype
Piersma, Bram
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Publication date: 2017
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Piersma, B. (2017). Biochemical and biomechanical regulation of the myofibroblast phenotype: focus on Hippo and TGFβ signaling. Rijksuniversiteit Groningen.
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Biochemical and biomechanical regulation of
the myofibroblast phenotype
focus on Hippo and TGFβ signaling
Bram Piersma
2017
The research in this thesis was performed at the Graduate School of Medical Sciences (GSMS) at the University of Groningen.
This PhD project was financially supported by the Netherlands Institute for Regenerative Medicine (NIRM) and the Dutch Kidney Foundation.
Biochemical and Biomechanical Regulation of the Myofibroblast Phenotype Focus on Hippo and TGFβ signaling
Piersma, B
Proefschrift Groningen
ISBN (eBook): 978-90-367-9625-5 ISBN (printed): 978-90-367-9624-8
Printing of this thesis was generously supported by:
Graduate School of Medical Sciences (GSMS) at the University of Groningen University Medical Center Groningen
University of Groningen
Cover design: Bram Piersma Lay-out: Bram Piersma Printed by IPSKAMP printing © Copyright 2017 B. Piersma
All rights reserved. No part of this publication may be reproduced, stored on a retrieval system, or transmitted in any form or by any means, without written permission of the author.
Biochemical and biomechanical regulation of
the myofibroblast phenotype
focus on Hippo and TGFβ signaling
Proefschrift
ter verkrijging van de graad van doctor aan de
Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. E. Sterken
en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
woensdag 5 april 2017 om 14:30 uur
door
Bram Piersma
geboren op 15 oktober 1986
te Zwolle.
Promotor
Prof. dr. R.A. Bank
Copromotor
Dr. M. Boersema
Beoordelingscommissie
Prof. dr. H. van Goor
Prof. dr. P. Olinga
Paranimfen
Mw. Cynthia Wellinga
Dhr. dr. Rutger A.F. Gjaltema
7 CHAPTER 1
Introduction and aim of this thesis CHAPTER 2
YAP1 is a driver of myofibroblast differentiation in normal and diseased fibroblasts
CHAPTER 3
Signaling in fibrosis: TGFβ, WNT, and YAP/TAZ converge CHAPTER 4
YAP synergizes with the TGFβ/Smad axis to regulate pro-fibrotic signaling
CHAPTER 5
αII-spectrin and βII-spectrin do not affect fibroblast mechanosensing and TGFβ1-induced myofibroblast differentiation
CHAPTER 6
Ascorbic acid promotes a TGFβ1-induced myofibroblast phenotype switch
CHAPTER 7
Summary and general discussion CHAPTER 8
Nederlandse samenvatting APPENDICES
Abbreviations
Curriculum Vitae and list of publications Dankwoord 9 27 51 77 99 119 135 147 155
