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Gene Expression and Variation in Keloid Fibroblasts

瘢痕疙瘩成纤维细胞的基因表达和变异

基本信息

批准号：
7008589
负责人：
Shirley B. Russell
金额：
$ 6.11万
依托单位：
MIDDLE TENNESSEE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-01-01 至 2007-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7008589
关键词：
African American cytokine family genetics fibroblasts gene expression genetic susceptibility glucocorticoids human tissue immunogenetics keloid skin disorder microarray technology polymerase chain reaction single nucleotide polymorphism tissue /cell culture transforming growth factors

项目摘要

DESCRIPTION (provided by applicant): Our hypothesis is that fibroblasts from keloids and other fibroproliferative diseases that disproportionately affect individuals of African ancestry exhibit an altered pattern of gene expression that predisposes them to fibrosis. Microarray analysis will be used to identify a spectrum of genes that shows altered expression in keloid fibroblasts. Analysis of differentially expressed genes will be used to generate hypotheses concerning involvement of these genes in our previously reported differences in growth and matrix synthesis in response to glucocorticoids, phorbol ester tumor promoters, and TGF-beta, and to test the hypothesis that the disproportionately high occurrence of fibrosis in the population involves altered production and/or response to Th2 cytokines. Analysis of polymorphisms in genes that are likely to play roles in TGF-beta, glucocorticoid, and Th2 cytokine pathways will be used to examine possible associations between particular sequences and fibrosis in individuals of African ancestry. Future linkage studies based on our findings will be aimed at identifying cis- and trans-acting genes that create a susceptibility to fibrosis.

描述(申请人提供)：我们的假设是，瘢痕疙瘩和其他纤维增生性疾病的成纤维细胞不成比例地影响非洲血统的个人，表现出基因表达模式的改变，使他们容易发生纤维化。微阵列分析将被用来识别在瘢痕疙瘩成纤维细胞中显示表达变化的一系列基因。对差异表达基因的分析将被用来产生关于这些基因参与我们之前报道的糖皮质激素、佛波酯肿瘤促进剂和转化生长因子-β反应的生长和基质合成差异的假说，并检验这一假说，即人群中不成比例的高纤维化发生率涉及Th2细胞因子的产生和/或反应的改变。对可能在转化生长因子-β、糖皮质激素和Th2细胞因子途径中起作用的基因的多态分析将被用来检查特定序列与非洲血统个体纤维化之间的可能联系。根据我们的发现，未来的连锁研究将致力于识别导致纤维化易感性的顺式和反式作用基因。