- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Theses and Dissertations /
- The role of small leucine-rich proteoglycans in non-scarring...
Open Collections
UBC Theses and Dissertations
UBC Theses and Dissertations
The role of small leucine-rich proteoglycans in non-scarring human oral mucosal wound healing Honardoust, Dariush
Abstract
Small leucine-rich proteoglycans (SLRPs) decorin, biglycan, fibromodulin and lumican are extracellular matrix (ECM) molecules that regulate collagen fibrilogenesis, cell functions and activity of transforming growth factor-P (TGF-ß). Thus, SLRPs may play critical roles in wound healing. In contrast to dermal wounds, gingival wounds regenerate with minimal scaring. However, the cellular and molecular mechanisms involved in this processes are not known. The aim of this study was to analyze the abundance of SLRPs, TGF-ß and Endo180, the major collagen endocytosis receptor in fibroblasts, in normal unwounded gingiva and during wound healing. The association of Endo180 with decorin was also investigated during wound healing. We hypothesized that compared to normal unwounded tissue, gingiva shows distinct localization and altered accumulation of SLRPs, TGF-ß and Endo180 during wound healing. To further analyze functions of SLRPs, we studied interaction of decorin with cultured gingival fibroblasts. Double immunostaining was used to study the localization of SLRPs, Endo180 or TGF-ß in tissue sections from normal human gingiva and up to 60 days after experimental wounding. The expression of Endo180 in cultured fibroblasts and keratinocytes was studied by immunoblotting and reverse transcriptase-polymerase chain reaction. To study interaction of cultured fibroblasts with decorin and decorin-induced signaling we used immunoblotting, function-blocking antibodies, pharmacological inhibitors, quantitative immunocytochemistry and RNA interference. In normal gingiva and during wound healing, SLRPs localized to collagen in a sitespecific manner. The immunoreactivity of SLRPs, TGF-ß1, TGF-ß3 and Endo180 was spatially and temporally regulated in myofibroblasts, pericytes, macrophages, endothelial and epithelial cells during wound healing. During wound healing, decorin colocalized with Endo180 in myofibroblasts. In cultured fibroblasts, decorin induced phosphorylation of distinct receptor tyrosine kinases leading to formation of reactive oxygen species (ROS) via the PI3K/mTOR signaling pathway. This was necessary for decorin endocytosis mainly via the clathrin-pathway. SLRPs may play a role in gingival wound re-epithelialization, collagen fibrilogenesis, ECM remodeling and cell signaling. Specifically, increased abundance of fibromodulin, decorin and TTGF-ß3 relative toTGF-ß1 may contribute to the reduced scaring during gingival wound healing. Decorin may interact with Endo180 to modulate its function and regulates cell signaling by inducing ROS formation.
Item Metadata
Title |
The role of small leucine-rich proteoglycans in non-scarring human oral mucosal wound healing
|
Creator | |
Publisher |
University of British Columbia
|
Date Issued |
2008
|
Description |
Small leucine-rich proteoglycans (SLRPs) decorin, biglycan, fibromodulin and lumican are
extracellular matrix (ECM) molecules that regulate collagen fibrilogenesis, cell functions and
activity of transforming growth factor-P (TGF-ß). Thus, SLRPs may play critical roles in wound
healing. In contrast to dermal wounds, gingival wounds regenerate with minimal scaring.
However, the cellular and molecular mechanisms involved in this processes are not known. The
aim of this study was to analyze the abundance of SLRPs, TGF-ß and Endo180, the major
collagen endocytosis receptor in fibroblasts, in normal unwounded gingiva and during wound
healing. The association of Endo180 with decorin was also investigated during wound healing.
We hypothesized that compared to normal unwounded tissue, gingiva shows distinct localization
and altered accumulation of SLRPs, TGF-ß and Endo180 during wound healing. To further
analyze functions of SLRPs, we studied interaction of decorin with cultured gingival fibroblasts.
Double immunostaining was used to study the localization of SLRPs, Endo180 or TGF-ß
in tissue sections from normal human gingiva and up to 60 days after experimental wounding.
The expression of Endo180 in cultured fibroblasts and keratinocytes was studied by
immunoblotting and reverse transcriptase-polymerase chain reaction. To study interaction of
cultured fibroblasts with decorin and decorin-induced signaling we used immunoblotting,
function-blocking antibodies, pharmacological inhibitors, quantitative immunocytochemistry and
RNA interference.
In normal gingiva and during wound healing, SLRPs localized to collagen in a sitespecific
manner. The immunoreactivity of SLRPs, TGF-ß1, TGF-ß3 and Endo180 was spatially
and temporally regulated in myofibroblasts, pericytes, macrophages, endothelial and epithelial
cells during wound healing. During wound healing, decorin colocalized with Endo180 in
myofibroblasts. In cultured fibroblasts, decorin induced phosphorylation of distinct receptor
tyrosine kinases leading to formation of reactive oxygen species (ROS) via the PI3K/mTOR
signaling pathway. This was necessary for decorin endocytosis mainly via the clathrin-pathway.
SLRPs may play a role in gingival wound re-epithelialization, collagen fibrilogenesis,
ECM remodeling and cell signaling. Specifically, increased abundance of fibromodulin, decorin
and TTGF-ß3 relative toTGF-ß1 may contribute to the reduced scaring during gingival wound
healing. Decorin may interact with Endo180 to modulate its function and regulates cell signaling
by inducing ROS formation.
|
Extent |
46893526 bytes
|
Genre | |
Type | |
File Format |
application/pdf
|
Language |
eng
|
Date Available |
2008-12-04
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
|
DOI |
10.14288/1.0066827
|
URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
|
Graduation Date |
2008-11
|
Campus | |
Scholarly Level |
Graduate
|
Rights URI | |
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International