Evaluation of global differential gene and protein expression in primary Pterygium: S100A8 and S100A9 as possible drivers of a signaling network.
Evaluation of global differential gene and protein expression in primary Pterygium: S100A8 and S100A9 as possible drivers of a signaling network.
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DOI：
10.1371/journal.pone.0097402
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tong L
中科院分区：
文献类型：
--
作者：
Hou A;Lan W;Law KP;Khoo SC;Tin MQ;Lim YP;Tong L
翼状胬肉是一种生长在眼表的翼状纤维血管，以纤维化、血管生成、细胞外基质重塑和炎性浸润为特征。流行病学研究已将翼状胬肉的形成与各种慢性炎症情况联系起来，如紫外线辐射、木屑暴露和干眼病。本研究的目的是利用基因芯片和蛋白质组学平台相结合的方法，寻找在原发性翼状胬肉中差异表达的蛋白质。使用基因芯片微阵列评估了四名患者的成对翼状胬肉和未受累的结膜组织的全球基因转录水平的差异。从另外四对组织中提取的蛋白质用iTRAQ方法进行定量。对其他患者进行免疫印迹和免疫荧光染色，以验证从微阵列和蛋白质组学数据中获得的异常蛋白表达。另外，用重组S100A8和/或S100A9处理原代结膜成纤维细胞。实时荧光定量聚合酶链式反应检测一组潜在靶基因的转录水平变化。S100、A8和A9、乙醛脱氢酶3家族、成员1(ALDH3A1)和波形蛋白(Vim)在蛋白和转录水平均有上调。相反，丝氨酸肽酶抑制剂A分支1(SERPINA1)和转铁蛋白(Tf)表达下调。加入S100A8和/或S100A9后，炎性趋化因子CXCL1、基质蛋白Vimentin、Biglycan、明胶蛋白以及膜联蛋白A2、胸腺肽β4、RAS癌基因家族成员CmA1和SERPINA1表达上调。通过比较基因芯片和蛋白质组数据，我们鉴定了3个上调的蛋白质和2个下调的蛋白质。在用S100A8/9刺激细胞时，在这些细胞中诱导了一系列在翼状胬肉组织中上调的关键基因。S100A8/9可能是翼状胬肉炎症和其他疾病途径的上游触发因素。
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. 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. 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. 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.
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影响因子：
4.4
作者：
Chong, Poh Kuan;Lee, Huiyin;Zhou, Jianbiao;Liu, Shaw-Cheng;Loh, Marie Chiew Shia;Wang, Ting Ting;Chan, Siew Pang;Smoot, Duane T.;Ashktorab, Hassan;So, Jimmy Bok Yan;Lim, Khong Hee;Yeoh, Khay Guan;Lim, Yoon Pin
通讯作者：
Lim, Yoon Pin
影响因子：
3.4
作者：
Chong, Poh-Kuan;Lee, Huiyin;Loh, Marie Chiew Shia;Choong, Lee-Yee;Lin, Qingsong;So, Jimmy Bok Yan;Lim, Khong Hee;Soo, Ross Andrew;Yong, Wei Peng;Chan, Siew Pang;Smoot, Duane T.;Ashktorab, Hassan;Yeoh, Khay Guan;Lim, Yoon Pin
通讯作者：
Lim, Yoon Pin
影响因子：
4.8
作者：
Harrison, CA;Raftery, MJ;Geczy, CL
通讯作者：
Geczy, CL
影响因子：
4.4
作者：
Di Girolamo, N;Coroneo, MT;Wakefield, D
通讯作者：
Wakefield, D
影响因子：
7.4
作者：
Gomes, Lincoln H.;Raftery, Mark J.;Geczy, Carolyn L.
通讯作者：
Geczy, Carolyn L.