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Characterization of transforming growth factor-β1 in β2 adrenergic receptor dysfunction and signaling mechanisms in human airway smooth muscle
Descriptive
TitleInfo
Title
Characterization of transforming growth factor-β1 in β2 adrenergic receptor dysfunction and signaling mechanisms in human airway smooth muscle
Name
(type = personal)
NamePart
(type = family)
Chung
NamePart
(type = given)
Elena
NamePart
(type = date)
1995
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Chung, Elena, 1995-
Role
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(authority = RULIB);
(type = text)
author
Name
(type = personal)
NamePart
(type = family)
Panettieri
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(type = given)
Reynold A
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Reynold A Panettieri
Affiliation
Advisory Committee
Role
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(authority = RULIB)
chair
Name
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NamePart
(type = family)
GOW
NamePart
(type = given)
ANDREW
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ANDREW GOW
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Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Jude
NamePart
(type = given)
Joseph
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Joseph Jude
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Koziol-White
NamePart
(type = given)
Cynthia J
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Cynthia J Koziol-White
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
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NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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School of Graduate Studies
Role
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school
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Text
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theses
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2020
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2020-05
Language
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(authority = ISO 639-3:2007);
(type = text)
English
Abstract
(type = abstract)
Underlying source(s) of airway smooth muscle hypercontractility and hyporesponsiveness
to bronchodilatory therapy in the context of inflammatory diseases of the lung remain
unclear. In asthma and chronic obstructive pulmonary disease (COPD), it is unclear if the
airway dysfunction is due to intrinsic genetic or epigenetic contribution that precipitate
increased basal tone and enhanced contractile responses, or attenuated bronchodilation
capability of the airways. Airway smooth muscle (ASM) cells are primary cells modulating
bronchomotor tone, but that alterations in the cells may be a primary contributor to airway
dysfunction associated with asthma and COPD. Studies suggest that β-adrenergic receptor
(β2AR) dysfunction in the inflammatory environment occurs via exposure to inflammatory
cytokines including exposure to IL-1β, IL-13, TNFα, and TGF-β, and lipid mediators. The
purpose of this thesis was to characterize β2AR dysfunction within the context of TGF-β1
exposure, as well as to characterize responsiveness to dexamethasone, a glucocorticoid.
Modulation of gene expression, cyclic AMP (cAMP) levels, and myosin light chain (MLC)
phosphorylation have been posited to play important roles in regulating both bronchoconstriction and bronchodilation in asthma. Furthermore, β2AR agonists (β2-
agonists), and both direct and indirect signaling components downstream of the receptor,
are effective treatments for asthma and other inflammatory conditions to induce relaxation
of the airways. However, persistent usage of these therapeutics causes desensitization and
downregulation of the receptor. Overall, the focus of this thesis is examining the efficacy
of bronchodilators in the context of TGF-β1 exposure, as well as the effects of
dexamethasone in modulating the effects of TGF-β1.
to bronchodilatory therapy in the context of inflammatory diseases of the lung remain
unclear. In asthma and chronic obstructive pulmonary disease (COPD), it is unclear if the
airway dysfunction is due to intrinsic genetic or epigenetic contribution that precipitate
increased basal tone and enhanced contractile responses, or attenuated bronchodilation
capability of the airways. Airway smooth muscle (ASM) cells are primary cells modulating
bronchomotor tone, but that alterations in the cells may be a primary contributor to airway
dysfunction associated with asthma and COPD. Studies suggest that β-adrenergic receptor
(β2AR) dysfunction in the inflammatory environment occurs via exposure to inflammatory
cytokines including exposure to IL-1β, IL-13, TNFα, and TGF-β, and lipid mediators. The
purpose of this thesis was to characterize β2AR dysfunction within the context of TGF-β1
exposure, as well as to characterize responsiveness to dexamethasone, a glucocorticoid.
Modulation of gene expression, cyclic AMP (cAMP) levels, and myosin light chain (MLC)
phosphorylation have been posited to play important roles in regulating both bronchoconstriction and bronchodilation in asthma. Furthermore, β2AR agonists (β2-
agonists), and both direct and indirect signaling components downstream of the receptor,
are effective treatments for asthma and other inflammatory conditions to induce relaxation
of the airways. However, persistent usage of these therapeutics causes desensitization and
downregulation of the receptor. Overall, the focus of this thesis is examining the efficacy
of bronchodilators in the context of TGF-β1 exposure, as well as the effects of
dexamethasone in modulating the effects of TGF-β1.
Subject
(authority = local)
Topic
Glucocorticoids
Subject
(authority = RUETD)
Topic
Toxicology
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
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ETD
Identifier
ETD_10901
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application/pdf
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text/xml
Extent
1 online resource (viii, 116 pages)
Note
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M.S.
Note
(type = bibliography)
Includes bibliographical references
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Title
School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/t3-b4pd-5925
Genre
(authority = ExL-Esploro)
ETD graduate
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Chung
GivenName
Elena
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2020-04-30 14:38:04
AssociatedEntity
Name
Elena Chung
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2020-05-06T12:20:38
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