Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery.
Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery.
复制标题
DOI：
10.1038/s41598-017-05780-5
复制
发表时间：
2017-07-17
影响因子：
4.6
通讯作者：
Khaw PT
中科院分区：
文献类型：
--
作者：
Yu-Wai-Man C;Owen N;Lees J;Tagalakis AD;Hart SL;Webster AR;Orengo CA;Khaw PT
纤维化相关事件在全球大多数致盲疾病中发挥着一定作用。然而，人们对这种复杂的多因素疾病的驱动机制知之甚少。我们在这里开展了第一个人类结膜纤维化的全基因组 RNA 测序研究。我们分别从既往接受过青光眼手术和未接受过青光眼手术的患者体内分离出 10 个原发性纤维化和 7 个非纤维化结膜成纤维细胞系。这些患者的种族和年龄相匹配。我们鉴定了 246 个基因，其差异表达超过两倍且 p<0.05，其中与非纤维化细胞系相比，其中 46 个基因在纤维化细胞系中上调，200 个基因下调。我们还进行了详细的基因本体论、KEGG、疾病关联、通路共享、WikiPathways 和蛋白质网络分析，并确定了与平滑肌收缩、炎症细胞因子、免疫介质、细胞外基质蛋白和癌基因表达相关的不同通路。我们进一步使用实时定量 PCR 验证了 11 个高度上调或下调的基因，发现 RNA-Seq 和 qPCR 结果之间存在很强的相关性。我们的研究表明，青光眼手术后结膜中存在明显的纤维化基因特征，并为驱动眼睛和其他组织中复杂纤维化过程的机制途径提供了新的见解。
Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
5.3
作者：
Eyden B
通讯作者：
Eyden B
影响因子：
4.8
作者：
Banerjee, S;Saxena, N;Banerjee, SK
通讯作者：
Banerjee, SK
影响因子：
32.4
作者：
Fielding, Ceri A.;Jones, Gareth W.;McLoughlin, Rachel M.;McLeod, Louise;Hammond, Victoria J.;Uceda, Javier;Williams, Anwen S.;Lambie, Mark;Foster, Thomas L.;Liao, Chia-Te;Rice, Christopher M.;Greenhill, Claire J.;Colmont, Chantal S.;Hams, Emily;Coles, Barbara;Kift-Morgan, Ann;Newton, Zarabeth;Craig, Katherine J.;Williams, John D.;Williams, Geraint T.;Davies, Simon J.;Humphreys, Ian R.;O'Donnell, Valerie B.;Taylor, Philip R.;Jenkins, Brendan J.;Topley, Nicholas;Jones, Simon A.
通讯作者：
Jones, Simon A.
影响因子：
3.6
作者：
Dees, Clara;Chakraborty, Debomita;Distler, Joerg H. W.
通讯作者：
Distler, Joerg H. W.