Chronic mucus hypersecretion in COPD and asthma: Involvement of microRNAs and stromal cell-epithelium crosstalk

Hataitip Tasena

Chronic mucus hypersecretion in COPD and asthma: Involvement of microRNAs and stromal cell-epithelium crosstalk

Hataitip Tasena

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Chronische obstructieve longziekte (COPD) is één van de belangrijkste doodsoorzaken wereldwijd, vooral bij ouderen. Astma is de meest voorkomende chronische ziekte bij kinderen. Veel COPD en astmapatiënten lijden aan chronische hoestklachten met overmatige slijmproductie, ook wel chronische mucus-hypersecretie (CMH) genoemd. Patiënten met CMH hebben een lagere kwaliteit van leven, meer ademhalingsmoeilijkheden en een hogere kans op overlijden. CMH wordt toegeschreven aan overmatige slijmproductie in de luchtwegen en verminderde mucusklaring.

In dit proefschrift is de hypothese getoetst dat micro-RNAs (miRNAs), kleine moleculen die vertaling van genen naar eiwitten reguleren, betrokken zijn bij CMH via het beïnvloeden van 1) de slijmproductie en 2) de communicatie tussen de slijmproducerende cellen in de luchtwegen en de onderliggen bindweefselcellen.

Door middel van uitgebreid profileren van miRNAs en afgeschreven genen in luchtwegbiopten, zijn nieuwe miRNAs en genen geïdentificeerd die mogelijk een rol spelen bij de ontwikkeling van CMH. microRNA-31-5p was gecorreleerd met CMH in zowel COPD en astma patiënten, wat er op duidt dat een soortgelijk mechanisme bijdraagt aan CMH in deze ziekten. Verder werd aangetoond dat er sprake is van communicatie tussen de bindweefselcellen die onder de slijmproducerende cellen liggen in de luchtwegen en dat deze communicatie de slijmproductie bevordert. Bovendien is aangetoond dat bij deze communicatie ook miRNAs, waaronder microRNA-146a-5p, betrokken zijn.

Met deze bevindingen is meer inzicht verkregen in de mechanismen die een rol spelen bij CMH in de context van zowel COPD als astma. Deze ontdekkingen met vertaling naar de kliniek leiden mogelijk tot de ontwikkeling van nieuwe therapeutische strategieën voor CMH.

Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Heijink, Irene, Supervisor Timens, Wim, Supervisor Brandsma, Corry-Anke, Co-supervisor van den Berge, Maarten, Co-supervisor
Datum van toekenning	3-jul.-2019
Plaats van publicatie	[Groningen]
Uitgever	University of Groningen
Gedrukte ISBN's	978-94-034-1704-2
Elektronische ISBN's	978-94-034-1703-5
Status	Published - 2019

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Title and contentsFinal publisher's version, 361 KB
Chapter 1Final publisher's version, 557 KB
Chapter 2Final publisher's version, 744 KB
Chapter 3Final publisher's version, 2,37 MB
Chapter 4Final publisher's version, 961 KB
Chapter 5Final publisher's version, 1,29 MB
Chapter 6Final publisher's version, 632 KB
Chapter 7Final publisher's version, 947 KB
Chapter 8Final publisher's version, 1,49 MB
Chapter 9Final publisher's version, 772 KB
Chapter 10Final publisher's version, 302 KB
Chapter 11Final publisher's version, 405 KB
AppendixFinal publisher's version, 293 KB
Complete thesisFinal publisher's version, 6,92 MB
PropositionsFinal publisher's version, 66,6 KB

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title = "Chronic mucus hypersecretion in COPD and asthma: Involvement of microRNAs and stromal cell-epithelium crosstalk",

abstract = "Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, especially in the elderly, while asthma is the most common chronic disease among children. Many COPD and asthma patients suffer from chronic cough with phlegm, a symptom called chronic mucus hypersecretion (CMH). Patients with CMH have a lower quality of life, more breathing difficulty, and a higher risk of death. CMH is attributed to excessive mucus production in the airways and impaired mucus clearance. In this thesis, we hypothesized that microRNAs (small molecules that regulate translation of genes into proteins) are involved in CMH by influencing 1) mucus production and 2) communication between mucus-producing cells in the airways and the cells in the underlying connective tissues.Through extensive profiling of miRNAs and transcribed genes in airway biopsies, new microRNAs and genes that potentially play a role in the development of CMH were identified. MicroRNA-31-5p was associated with CMH in both COPD and asthma, suggesting a similar mechanism that contributes to CMH in both diseases. Furthermore, we showed that the cells in the underlying connective tissues communicate with mucus-producing cells in the airway, and this communication promotes mucus production. It was also shown that microRNAs, including miRNA-146a-5p, are also involved in this communication.The findings in this thesis provide more insight into mechanisms that play a role in CMH in the contexts of both COPD and asthma. The translation of these discoveries to the clinic may lead to the development of new treatment strategies for CMH.",

author = "Hataitip Tasena",

year = "2019",

language = "English",

isbn = "978-94-034-1704-2",

publisher = "University of Groningen",

school = "University of Groningen",

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TY - BOOK

T1 - Chronic mucus hypersecretion in COPD and asthma

T2 - Involvement of microRNAs and stromal cell-epithelium crosstalk

AU - Tasena, Hataitip

PY - 2019

Y1 - 2019

N2 - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, especially in the elderly, while asthma is the most common chronic disease among children. Many COPD and asthma patients suffer from chronic cough with phlegm, a symptom called chronic mucus hypersecretion (CMH). Patients with CMH have a lower quality of life, more breathing difficulty, and a higher risk of death. CMH is attributed to excessive mucus production in the airways and impaired mucus clearance. In this thesis, we hypothesized that microRNAs (small molecules that regulate translation of genes into proteins) are involved in CMH by influencing 1) mucus production and 2) communication between mucus-producing cells in the airways and the cells in the underlying connective tissues.Through extensive profiling of miRNAs and transcribed genes in airway biopsies, new microRNAs and genes that potentially play a role in the development of CMH were identified. MicroRNA-31-5p was associated with CMH in both COPD and asthma, suggesting a similar mechanism that contributes to CMH in both diseases. Furthermore, we showed that the cells in the underlying connective tissues communicate with mucus-producing cells in the airway, and this communication promotes mucus production. It was also shown that microRNAs, including miRNA-146a-5p, are also involved in this communication.The findings in this thesis provide more insight into mechanisms that play a role in CMH in the contexts of both COPD and asthma. The translation of these discoveries to the clinic may lead to the development of new treatment strategies for CMH.

AB - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, especially in the elderly, while asthma is the most common chronic disease among children. Many COPD and asthma patients suffer from chronic cough with phlegm, a symptom called chronic mucus hypersecretion (CMH). Patients with CMH have a lower quality of life, more breathing difficulty, and a higher risk of death. CMH is attributed to excessive mucus production in the airways and impaired mucus clearance. In this thesis, we hypothesized that microRNAs (small molecules that regulate translation of genes into proteins) are involved in CMH by influencing 1) mucus production and 2) communication between mucus-producing cells in the airways and the cells in the underlying connective tissues.Through extensive profiling of miRNAs and transcribed genes in airway biopsies, new microRNAs and genes that potentially play a role in the development of CMH were identified. MicroRNA-31-5p was associated with CMH in both COPD and asthma, suggesting a similar mechanism that contributes to CMH in both diseases. Furthermore, we showed that the cells in the underlying connective tissues communicate with mucus-producing cells in the airway, and this communication promotes mucus production. It was also shown that microRNAs, including miRNA-146a-5p, are also involved in this communication.The findings in this thesis provide more insight into mechanisms that play a role in CMH in the contexts of both COPD and asthma. The translation of these discoveries to the clinic may lead to the development of new treatment strategies for CMH.

M3 - Thesis fully internal (DIV)

SN - 978-94-034-1704-2

PB - University of Groningen

CY - [Groningen]

ER -

Chronic mucus hypersecretion in COPD and asthma: Involvement of microRNAs and stromal cell-epithelium crosstalk

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