Evaluation of Global Differential Gene and Protein Expression in Primary Pterygium: S100A8 and S100A9 as Possible Drivers of a Signaling NetworkReportar como inadecuado




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Purpose

Pterygium is a wing shaped fibrovascular growth on the ocular surface, characterized by fibrosis, angiogenesis, extracellular matrix remodeling, and inflammatory infiltrates. Epidemiologic studies have linked pterygium formation to various chronic inflammatory conditions, such as ultraviolet radiation, sawdust exposure, and dry eye disease. The purpose of this study is to identify proteins that are differentially expressed in primary pterygium by using a combination of gene microarray and proteomic platforms.

Methods

Paired pterygium and uninvolved conjunctiva tissues of four patients were evaluated for differences in global gene transcript levels using a genechip microarray. Proteins extracted from another four pairs of tissues were quantified by iTRAQ approach. Western blot and immunofluorescent staining on additional patients were used to validate dysregulated protein expression obtained from microarray and proteomics data. In addition, primary conjunctival fibroblasts were treated with recombinant S100A8, S100A9 or both. Transcript level changes of a panel of potential target genes were evaluated by real time-PCR.

Results

The following were up-regulated at both protein and transcript levels S100 A8 and A9, aldehyde dehydrogenase 3 family, member1 ALDH3A1 and vimentin VIM. Conversely, serpin peptidase inhibitor clade A member 1 SERPINA1 and transferrin TF were down-regulated. Upon adding S100A8, S100A9 or both, the inflammatory chemokine CXCL1, matrix proteins vimentin, biglycan, and gelsolin, as well as annexin-A2, thymosin-β4, chymase CMA1, member of Ras oncogene family RAB10 and SERPINA1 were found to be up-regulated.

Conclusions

We identified 3 up-regulated and 2 down-regulated proteins by using a stringent approach comparing microarray and proteomic data. On stimulating cells with S100A8-9, a repertoire of key genes found to be up-regulated in pterygium tissue, were induced in these cells. S100A8-9 may be an upstream trigger for inflammation and other disease pathways in pterygium.



Autor: Aihua Hou , Wanwen Lan , Kai Pong Law, Ser Chin Jasmine Khoo, Min Qi Tin, Yoon Pin Lim, Louis Tong

Fuente: http://plos.srce.hr/



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