Role of prohibitin in intestinal inflammation

抑制素在肠道炎症中的作用

• 批准号: 7154371
• 负责人: ARIANNE L THEISS
• 金额: $ 4.6万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7154371
• 关键词: biological signal transduction; cell line; colitis; disease /disorder model; gastrointestinal epithelium; gene expression; gene targeting; immunoregulation; inflammation; inflammatory bowel diseases; interleukin 6; laboratory mouse; oxidative stress; postdoctoral investigator; protein structure function; transcription factor; wound healing

DESCRIPTION (provided by applicant): Prohibitin (PHB) is implicated to be involved in diverse cellular processes such as oxidative stress. The expression and function of PHB in the normal intestine and during intestinal inflammation are not known. Oxidative stress plays an important role in the pathogenesis of inflammatory bowel diseases due to its effects on mucosal barrier disruption and inflammation. Given the potential role of PHB in regulating oxidative stress during various physiological conditions, PHB may be involved in modulating oxidative stress associated with intestinal inflammation. The overall goal of this proposal is to characterize the regulation of PHB in intestinal epithelial cells and its role in modulating inflammation-induced oxidative stress and wound healing. The regulation of PHB expression by the immunoregulatory cytokine IL-6 will be studied. The role of PHB in oxidative stress and wound healing will be determined using an intestinal epithelial cell line over- or under-expressing PHB. Also, the in vivo effect of IL-6 knockout on PHB expression and wound healing will be assessed during experimental colitis. Thus, studies on PHB will lead to a better understanding of inflammation-induced oxidative stress and may lead to novel therapies for intestinal inflammatory disorders.

描述（由申请人提供）：Prohibitin（PHB）涉及多种细胞过程，如氧化应激。在正常肠道和肠道炎症过程中，PHB的表达和功能尚不清楚。氧化应激通过影响黏膜屏障的破坏和炎症反应，在炎症性肠病的发病机制中起重要作用。考虑到在各种生理条件下PHB在调节氧化应激中的潜在作用，PHB可能参与调节与肠道炎症相关的氧化应激。该提案的总体目标是表征肠道上皮细胞中的PHB的调节及其在调节炎症诱导的氧化应激和伤口愈合中的作用。将研究免疫调节细胞因子IL-6对PHB表达的调节。将使用过表达或低表达PHB的肠上皮细胞系来确定PHB在氧化应激和伤口愈合中的作用。此外，将在实验性结肠炎期间评估IL-6敲除对PHB表达和伤口愈合的体内作用。因此，对PHB的研究将导致更好地理解炎症诱导的氧化应激，并可能导致肠道炎症性疾病的新疗法。