■探讨眼表(OS)疾病慢性期病理性角质化的分子机制。
■在这项研究中,使用寡核苷酸微阵列对3例病理性角质化患者的OS上皮细胞进行了全面的基因表达分析(Stevens-Johnson综合征[n=1例],眼瘢痕性类天疱疮[n=1例],和前葡萄肿[n=1例])。对照组为3例结膜松弛症患者。使用定量实时PCR确认一些转录物中的表达。
■与对照相比,3118个基因在病理性角化上皮细胞中显著上调2倍或一半以上(方差分析P<0.05)。涉及角质化的基因,脂质代谢,氧化还原酶上调,而基因参与细胞反应,以及已知的转录因子(TFs),被下调。通过基因本体论分析和已知报道,进一步分析了这些基因与TF和视黄酸(RA)的关系。TFsMYBL2,FOXM1和SREBF2的表达上调,TFELF3显著下调。AKR1B15、RDH12和CRABP2的表达(即,与RA相关的基因,已知可以抑制角质化)增加了二十倍以上,而RARB和RARRES3基因的表达降低了1/50。CRABP2,RARB,和RARRES3表达变化也通过qRT-PCR证实。
■在病理性角化眼表中,常见的成绩单变化,包括维生素A代谢异常,参与病理性角质化的机制。
UNASSIGNED: To investigate the molecular mechanism of pathological keratinization in the chronic phase of ocular surface (OS) diseases.
UNASSIGNED: In this study, a comprehensive gene expression analysis was performed using oligonucleotide microarrays on OS epithelial cells obtained from three patients with pathological keratinization (Stevens-Johnson syndrome [n = 1 patient], ocular cicatricial pemphigoid [n = 1 patient], and anterior staphyloma [n = 1 patient]). The controls were three patients with conjunctivochalasis. The expression in some transcripts was confirmed using quantitative real-time PCR.
UNASSIGNED: Compared to the controls, 3118 genes were significantly upregulated by a factor of 2 or more than one-half in the pathological keratinized epithelial cells (analysis of variance P < 0.05). Genes involved in keratinization, lipid metabolism, and oxidoreductase were upregulated, while genes involved in cellular response, as well as known transcription factors (TFs), were downregulated. Those genes were further analyzed with respect to TFs and retinoic acid (RA) through gene ontology analysis and known reports. The expression of TFs MYBL2, FOXM1, and SREBF2, was upregulated, and the TF ELF3 was significantly downregulated. The expression of AKR1B15, RDH12, and CRABP2 (i.e., genes related to RA, which is known to suppress keratinization) was increased more than twentyfold, whereas the expression of genes RARB and RARRES3 was decreased by 1/50. CRABP2, RARB, and RARRES3 expression changes were also confirmed by qRT-PCR.
UNASSIGNED: In pathological keratinized ocular surfaces, common transcript changes, including abnormalities in vitamin A metabolism, are involved in the mechanism of pathological keratinization.