Role of MCH in Adipose Tissue & Intestinal Inflammation

MCH 在脂肪组织中的作用

• 批准号: 7158216
• 负责人: Kara Gross Margolis
• 金额: $ 5.4万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-31 至 2008-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7158216
• 关键词: adipose tissue; biological signal transduction; confocal scanning microscopy; disease /disorder etiology; enzyme activity; gene expression; hormone receptor; hormone regulation /control mechanism; hypothalamic hormones; immunocytochemistry; immunologic assay /test; inflammation; inflammatory bowel diseases; interleukin 8; intestinal mucosa; laboratory mouse; laser capture microdissection; melanins; mesentery; mitogen activated protein kinase; neuropeptides; nuclear factor kappa beta; pathologic process; pituitary hormones; postdoctoral investigator; protein structure function

DESCRIPTION (provided by applicant): Melanin-concentrating hormone (MCH), a hypothalamic neuropeptide that regulates appetite and body weight, has also been shown to play a proinflammatory role in colitis of various etiologies. Thus, mesenteric human preadipocytes express MCH receptors, and MCH binding to these receptors stimulates expression of IL-8, a neutrophil chemoattractant involved in IBD pathogenesis. Since patients with Crohn's disease have mesenteric fat wrapping of the bowel associated with increased expression of proinflammatory cytokines, it is likely that MCH participates in this inflammatory response. The goals of this study are two-fold: 1) To examine the hypothesis that MCH links mucosal inflammation with inflammatory changes in the mesenteric fat depots during colitis and 2) that NF-kB and MAP kinase pathways contribute to the signaling involved. This will be done by comparing MCH and MCH-receptor expression at the protein and mRNA levels in murine fat depots to degree of mucosal inflammation during TNBS-, DSS-, and IL-10 KO colitis, identifying the cells expressing MCH/MCHR1 in this tissue through laser capture microdissection, immunohistochemical analysis, and confocal microscopy and dissecting signalling pathways by western blot, RT-PCR and ELISA.

描述（由申请人提供）：一种调节食欲和体重的下丘脑神经肽的黑色素浓缩激素（MCH）也已被证明在各种病因的结肠炎中起促炎作用。因此，肠系膜人的前脂肪细胞表达MCH受体，MCH与这些受体的结合刺激了IL-8的表达，IL-8是IBD发病机理中涉及的中性粒细胞趋化剂。由于克罗恩病患者的肠道脂肪包裹与促炎细胞因子的表达增加有关，因此MCH可能会参与这种炎症反应。这项研究的目标是两个方面：1）检验以下假设：MCH将粘膜炎症与结肠炎期间肠系膜脂肪库的炎症变化联系在一起，以及2）NF-KB和MAP激酶途径有助于涉及信号传导。这将通过比较鼠脂肪仓库中蛋白质和mCH受体水平的MCH和MCH受体表达与TNBS-，DSS和IL-10 KO结肠炎期间的粘膜炎症程度与粘膜炎症程度，从而鉴定出通过激光通过激光捕获微型分解，免疫组织和共性组织，以及识别该组织中表达MCHR1的细胞RT-PCR和ELISA。