University of Groningen
Compartmentalized cAMP Signaling in COPD
Zuo, Haoxiao
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Publication date: 2019
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Zuo, H. (2019). Compartmentalized cAMP Signaling in COPD: Focus on Phosphodiesterases and A-Kinase Anchoring Proteins. University of Groningen.
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Compartmentalized cAMP Signaling in COPD
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 financially supported by the Ubbo Emmius program of the University of Groningen and by the Institute of Experimental Cardiovascular Research, University of Hamburg, Germany.
Printing of this thesis was fi nancially supported by: University of Groningen
Graduate School of Science (GSS) Faculty of Science and Engineering (FSE)
Paranimfen: Mariska P.M. van den Berg Sophie Bos
Thesis cover: Human Lung Cover design: Hendra Su
Lay-out: Haoxiao Zuo and Fred van der Spek | Ridderprint BV Printing: | www.ridderprint.nl
ISBN (printed): 978-94-034-1786-8
ISBN (electronic version): 978-94-034-1787-5
Copyright © H. Zuo, 2019
All rights reserved. No part of this book may be reproduced in any manner or by any means without permission.
Compartmentalized cAMP
Signaling in COPD
Focus on Phosphodiesterases and A-Kinase Anchoring Proteins
Phd thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus prof. E. Sterken
and in accordance with the decision by the College of Deans. This thesis will be defended in public on
Friday 28 June 2019 at 16.15 hours
by
Haoxiao Zuo
born on 19 January 1989 in Shandong, China
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 financially supported by the Ubbo Emmius program of the University of Groningen and by the Institute of Experimental Cardiovascular Research, University of Hamburg, Germany.
Printing of this thesis was fi nancially supported by: University of Groningen
Graduate School of Science (GSS) Faculty of Science and Engineering (FSE)
Paranimfen: Mariska P.M. van den Berg Sophie Bos
Thesis cover: Human Lung Cover design: Hendra Su
Lay-out: Haoxiao Zuo and Fred van der Spek | Ridderprint BV Printing: | www.ridderprint.nl
ISBN (printed): 978-94-034-1786-8
ISBN (electronic version): 978-94-034-1787-5
Copyright © H. Zuo, 2019
All rights reserved. No part of this book may be reproduced in any manner or by any means without permission.
Compartmentalized cAMP
Signaling in COPD
Focus on Phosphodiesterases and A-Kinase Anchoring Proteins
Phd thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus prof. E. Sterken
and in accordance with the decision by the College of Deans. This thesis will be defended in public on
Friday 28 June 2019 at 16.15 hours
by
Haoxiao Zuo
born on 19 January 1989 in Shandong, China
Supervisors
Prof. M. Schmidt Prof. V.O. NikolaevAssessment Committee
Prof. C. PageProf. G. Folkerts Prof. B.N. Melgert
Contents
CHAPTER 1 General Introduction 7
CHAPTER 2 Epac Function and cAMP Scaffolds in the Heart and Lung 17
CHAPTER 3 Phosphodiesterases As Therapeutic Targets for Respiratory Diseases 39
CHAPTER 4 Cigarette Smoke Upregulates PDE3 and PDE4 to Decrease cAMP in Airway Cells 81
CHAPTER 5 PDE8: a Novel Target in Human Airway Smooth Muscle Cells 111
CHAPTER 6 Function of cAMP Scaffolds in Obstructive Lung Disease: Focus on Epithelial-to-Mesenchymal Transition and Oxidative Stress 117
CHAPTER 7 A-Kinase Anchoring Proteins Diminish TGF-β1/Cigarette Smoke-Induced Epithelial-to-Mesenchymal Transition 141
CHAPTER 8 Cigarette Smoke Exposure Alters Phosphodiesterases in Structural Lung Cells 173
CHAPTER 9 General Discussion 185
CHAPTER 10 Nederlandse Samenvatting 199
Acknowledgements 207
Curriculum Vitae 215
Supervisors
Prof. M. Schmidt Prof. V.O. NikolaevAssessment Committee
Prof. C. PageProf. G. Folkerts Prof. B.N. Melgert
Contents
CHAPTER 1 General Introduction 7
CHAPTER 2 Epac Function and cAMP Scaffolds in the Heart and Lung 17
CHAPTER 3 Phosphodiesterases As Therapeutic Targets for Respiratory Diseases 39
CHAPTER 4 Cigarette Smoke Upregulates PDE3 and PDE4 to Decrease cAMP in Airway Cells 81
CHAPTER 5 PDE8: a Novel Target in Human Airway Smooth Muscle Cells 111
CHAPTER 6 Function of cAMP Scaffolds in Obstructive Lung Disease: Focus on Epithelial-to-Mesenchymal Transition and Oxidative Stress 117
CHAPTER 7 A-Kinase Anchoring Proteins Diminish TGF-β1/Cigarette Smoke-Induced Epithelial-to-Mesenchymal Transition 141
CHAPTER 8 Cigarette Smoke Exposure Alters Phosphodiesterases in Structural Lung Cells 173
CHAPTER 9 General Discussion 185
CHAPTER 10 Nederlandse Samenvatting 199
Acknowledgements 207
Curriculum Vitae 215
