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. / Dentistry, Faculty of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/2836 |
| Date | 11 1900 |
| Creators | Honardoust, Dariush |
| Publisher | University of British Columbia |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Format | 46893526 bytes, application/pdf |
| Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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