We have further demonstrated that RIPK4 is a direct transcriptional target of the protein p63, a master regulator of stratified epithelial development, which acts as a nodal point in the cascade of molecular events that prevent pterygium syndromes.
Furthermore, p70S6K knockdown and the specific mTOR inhibitor rapamycin decreased the expression levels of p-p70S6K and α-SMA in cultured fibroblasts from grade T3 pterygium.
Lower levels of antioxidant enzymes and non-enzymatic small molecules and higher levels of oxidative stress and inflammatory clinical parameters such as NO, MDA, <i>TNF-α</i> and MMP-9 may be involved in the pathogenesis of systemic chemotherapy related ocular complications such as cataract, glaucoma, blepharitis, retinitis pigmentosa, macular degeneration, pterygium and retinal degeneration.
Among these genes, we chose three proteins, aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1), protein disulfide-isomerase A3 (PDIA3), and peroxiredoxin-2 (PRDX2), that were significantly upregulated in pterygium and further increased in recurrent pterygium.
The increased level of 8-OHdG in pterygium is not due to decreased expression of hOGG1, while increased levels of 8-OHdG induced the expression of hOGG1.
Therefore, BPDE-like DNA adducts and CYP1A1 and GSTM1 polymorphisms were detected in this study to provide more molecular evidence to understand the cause of BPDE-like DNA adduct formation in pterygium.
Although, these results suggest that overexpression of peroxiredoxin 2 in pterygium could protect the cell against oxidative stress-induced apoptosis, further studies are required to establish the functional role of peroxiredoxin 2 in pterygium to determine its role in peroxidation and apoptosis in this pathology.
A dose- and time-dependent increase in MMP-1 was observed when pterygium epithelial cells were exposed to UVB with no significant modulation of inhibitor activity.
The most abundant complementary DNAs from pterygium include clusterin, keratins 13 (Krt13) and 4 (Krt4), S100A9/calgranulin B, and spermidine/spermine N1-acetyltransferase (SAT1).
Primary grade 2 pterygium (n=20) and normal conjunctiva (n=20) biopsies were obtained during surgery after written informed consent. mRNA expression for CD31, podoplanin, and VEGF (isoforms VEGF-A and VEGF-165) were determined by qRT-PCR.
The concerted down-regulation of four members from both clusters of the miR-200 family (miR-200a/-200b/-429 and miR-200c/-141), which are known to regulate EMT, and up-regulation of the predicted target and mesenchymal marker fibronectin (FN1), suggest that EMT could potentially play a role in the pathogenesis of pterygium and might constitute promising new targets for therapeutic intervention in pterygium.
Rosiglitazone suppresses TGF-β1-induced myofibroblast activation and extra cellular matrix synthesis in pterygium fibroblasts at least partly through the modulation of the p38 MAPK pathway.
SPARC was upregulated in pterygium and may collaborate with increased MMP-3 in some patients to account for many of the phenotypic properties characteristic of pterygium.
Several extracellular matrix constituents, LOXs, FBN1, and FBLN5, implicated in the development of elastin, are overexpressed in the subepithelial connective tissue extracellular matrix of human pterygium, supporting our hypothesis that elastic synthesis and reticulation is dysregulated in this type of pathology.
Increased tropoelastin staining was seen in the pterygium tissue with areas of degenerative changes or immature formation of elastic fibers, as well an increase in tropoelastin mRNA, in contrast with fibulin-2 and fibulin-3 messenger levels.
We examined the pathways responsible for enhanced expression of MMP-1 in pterygium epithelial cells after UVB exposure and/or treatment with chemical inhibitors of mitogen-activated protein kinases or epidermal growth factor receptor.
Sections from each pterygium were immunostained with CD31 and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) monoclonal antibodies to evaluate LMVD and blood microvessel density.
RhoA activity was significantly upregulated in pterygium fibroblast cells (PFCs) and UV-NCFCs, and myosin phosphatase-Rho interacting protein (MRIP) was upregulated, and myosin phosphatase target subunit 1 (MYPT1) was downregulated in PFCs.
The results reveal similar behaviors in limbal and pterygium epithelial cells in terms of VEGF and VEGFR expression, with the presumption that pterygia arise from limbal epithelial cells and that human conjunctivas are not a suitable control for the analysis of pterygia.