Dataset Information

Expression of insulin-like growth factor binding protein-3 in pterygium tissue.

ABSTRACT:

Background

Pterygium is a fibrovascular overgrowth from the conjunctiva onto the cornea. The pathogenesis of this common ocular surface disorder is not well understood and the only treatment is surgical removal.

Methods

DNA microarray analysis of primary pterygium tissue was carried out using uninvolved conjunctiva tissue as a comparison for gene expression levels. Real time polymerase chain reaction (PCR) was used to verify the mRNA level of expression for genes changed in pterygium. Western blot analysis and immunohistochemistry showed protein expression levels and the tissue distribution.

Results

Microarray analysis revealed that mRNA levels of a number of genes were changed in primary pterygium. In particular the gene for insulin-like growth factor binding protein-3, (IGFBP3), which modulates the effects of insulin-like growth factor on cells was significantly decreased. Both the message and protein expression of IGFBP3 in pterygium were decreased compared to normal, uninvolved conjunctiva.

Conclusion

Decreased levels of IGFBP3 protein have been strongly correlated with the presence of cancer. Identification of the low level of expression of IGFBP3 in pterygium suggests that the pathway controlling cell proliferation has lost an important control mechanism, which may explain the continued growth of pterygium.

SUBMITTER: Wong YW

PROVIDER: S-EPMC1860207 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

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Publications

Expression of insulin-like growth factor binding protein-3 in pterygium tissue.

Wong Y W YW Chew J J Yang H H Tan D T H DT Beuerman R R

The British journal of ophthalmology 20060217 6

<h4>Background</h4>Pterygium is a fibrovascular overgrowth from the conjunctiva onto the cornea. The pathogenesis of this common ocular surface disorder is not well understood and the only treatment is surgical removal.<h4>Methods</h4>DNA microarray analysis of primary pterygium tissue was carried out using uninvolved conjunctiva tissue as a comparison for gene expression levels. Real time polymerase chain reaction (PCR) was used to verify the mRNA level of expression for genes changed in pteryg ...[more]

PMID: 16488932

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Project description:PURPOSE: Pterygium is an ocular surface disease of unknown etiology associated with epithelial and fibrovascular outgrowth from the conjunctiva onto the cornea. S100 proteins are calcium-activated signaling proteins that interact with other proteins to modulate biological functions such as cell migration, proliferation, and differentiation. The aim of this study was to investigate the presence of various S100 proteins in pterygium compared to normal conjunctiva. METHODS: Immunofluorescent staining using antibodies against S100A4, S100A6, S100A8, S100A9, and S100A11 were conducted to investigate the expression and tissue distribution. S100 protein secretions and expressions were confirmed using western blot and quantitative real-time polymerase chain reaction (RT-PCR), respectively. RESULTS: Immunofluorescent staining demonstrated the presence of S100A4, S100A6, S100A8, S100A8, S100A9, and S100A11 in both conjunctival and pterygial epithelium. No significant difference was found in the localization and expression of S100A4. In both conjunctiva and pterygium, S100A4-positive cells were found in superficial and suprabasal layers. S100A6 expression was strong in the superficial layer of pterygium epithelium but relatively weaker in the suprabasal and superficial cells of normal conjunctiva epithelium. S100A8 and S100A9 were localized in the superficial layer of both pterygium and normal conjunctiva epithelium, with higher levels in pterygium than uninvolved conjunctiva. S100A11 was expressed in the basal cells of conjunctival epithelium but in the suprabasal layers of pterygium epithelium. Western blot and RT-PCR confirmed the presence of S100A4, S100A6, S100A8, S100A9, and S100A11 in pterygium and conjunctiva tissue. CONCLUSIONS: Higher levels of S100A6, S100A8, and S100A9 expressions were detected in the pterygium tissue relative to normal conjunctiva. In addition, a distinct alteration of localization of S100A11 expression was observed in pterygium epithelium compared to the conjunctiva. Therefore, these S100 proteins may be associated with the formation of pterygium.

Project description:To characterize predictors of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in acute critical illness with the hypothesis that acute factors associated with critical illness will more strongly predict circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 than chronic clinical or genetic factors.Observational study nested within a large prospective study using multivariable linear regression to model circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 with acute and chronic clinical variables, and genotype from five polymorphisms in insulin-like growth factor pathway genes.ICUs from two large academic medical centers.Five hundred forty-three Caucasian patients with risk factors for acute respiratory distress syndrome and available plasma from early in critical illness.None.Total insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 were measured in plasma using IMMULITE assays (Siemens, Malvern, PA). We examined age, gender, body mass index, cirrhosis, and diabetes, as well as Acute Physiology, Age, and Chronic Health Evaluation III score, acute hepatic dysfunction, pneumonia and aspiration, sepsis/septic shock, acute respiratory distress syndrome, and receipt of corticosteroids. Body mass index, cirrhosis, and acute respiratory distress syndrome were strongly associated with insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels; Acute Physiology, Age, and Chronic Health Evaluation III was strongly associated with insulin-like growth factor-1 levels; and age was strongly associated with insulin-like growth factor-binding protein-3. Five polymorphisms (IGF1: rs1520220, rs35767, rs2946834; IGFBP1: rs4619; IGFBP3: rs2854746) were analyzed for associations with plasma levels. When genotypes were added to models, rs2854746 was significantly associated with plasma insulin-like growth factor-binding protein-3. Genotype explained an additional 2% of variability with an overall adjusted R-square of 0.18.Despite the acute derangements of critical illness, both acute and chronic health factors significantly influence circulating levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 early in critical illness. rs2854746 is also significantly associated with insulin-like growth factor-binding protein-3 levels in this ICU cohort. Overall, phenotypic and genotypic factors explained only a modest amount of variability in insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. Further research is needed to understand how to apply these findings to patient care.

Dataset Information

Expression of insulin-like growth factor binding protein-3 in pterygium tissue.

Background

Methods

Results

Conclusion

Publications

Expression of insulin-like growth factor binding protein-3 in pterygium tissue.

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