Systematic identification and characterization of novel human skin-associated genes encoding membrane and secreted proteins.
Systematic identification and characterization of novel human skin-associated genes encoding membrane and secreted proteins.
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DOI：
10.1371/journal.pone.0063949
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zlotnik A
中科院分区：
文献类型：
--
作者：
Gerber PA;Hevezi P;Buhren BA;Martinez C;Schrumpf H;Gasis M;Grether-Beck S;Krutmann J;Homey B;Zlotnik A
通过对代表105种不同组织和细胞类型的人类基因表达数据库的生物信息学分析，我们确定了687个在人类皮肤中选择性和高度表达的皮肤相关基因。其中超过50个代表以前与皮肤无关的未表征基因，包括编码新型分泌和质膜蛋白的子集。这些新的治疗靶基因中的八个的高水平皮肤相关表达通过正常皮肤和皮肤衍生细胞系的半定量真实的时间PCR、蛋白质印迹和免疫组织化学分析来证实。其中四种由表皮角质形成细胞特异性表达;两种编码G蛋白偶联受体（GPR 87和GPR 115），两种编码分泌蛋白（WFDC 5和SERPINB 7）。进一步的分析，使用精氨酸激活和终末分化的人原代角质形成细胞或一组常见的炎症，自身免疫性或恶性皮肤疾病揭示了不同的模式的调节以及疾病的关联，指出在皮肤稳态和疾病的重要作用。这些新的未表征的皮肤基因中的一些可能代表用于未来诊断或治疗的开发的潜在生物标志物或药物靶点。
Through bioinformatics analyses of a human gene expression database representing 105 different tissues and cell types, we identified 687 skin-associated genes that are selectively and highly expressed in human skin. Over 50 of these represent uncharacterized genes not previously associated with skin and include a subset that encode novel secreted and plasma membrane proteins. The high levels of skin-associated expression for eight of these novel therapeutic target genes were confirmed by semi-quantitative real time PCR, western blot and immunohistochemical analyses of normal skin and skin-derived cell lines. Four of these are expressed specifically by epidermal keratinocytes; two that encode G-protein-coupled receptors (GPR87 and GPR115), and two that encode secreted proteins (WFDC5 and SERPINB7). Further analyses using cytokine-activated and terminally differentiated human primary keratinocytes or a panel of common inflammatory, autoimmune or malignant skin diseases revealed distinct patterns of regulation as well as disease associations that point to important roles in cutaneous homeostasis and disease. Some of these novel uncharacterized skin genes may represent potential biomarkers or drug targets for the development of future diagnostics or therapeutics.
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影响因子：
--
作者：
Gugger M;White R;Song S;Waser B;Cescato R;Rivière P;Reubi JC
通讯作者：
Reubi JC
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP
影响因子：
--
作者：
Colpitts, TL;Billing, P;Stroupe, S
通讯作者：
Stroupe, S
影响因子：
5.5
作者：
Harder, J;Schröder, JM
通讯作者：
Schröder, JM
影响因子：
3
作者：
Chassain, C;Eschalier, A;Durif, F
通讯作者：
Durif, F