半乳糖凝集素- 12在脂肪細胞引起的發炎反應所扮演的角色

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題名:	半乳糖凝集素- 12在脂肪細胞引起的發炎反應所扮演的角色
作者:	萬磊(Lei Wan)
貢獻者:	中醫學院中醫學系學士班中醫基礎學科;中國附醫醫研部婦科
關鍵詞:	半乳?凝集素12;脂肪組織;發炎反應;T 細胞;巨噬細胞;Galectin-12;adipose tissue;inflammation;T cell;macrophage
日期:	2013-07-31
上傳時間:	2013-10-17 11:08:03 (UTC+8)
摘要:	半乳?凝集素是一群能與半乳?結合的蛋白。半乳?凝集素 12 包含?個? 同的醣結合位置，雖然沒有直接證明其與半乳?結合的能?，但根據序?上的相似性，它被認為是屬於半乳?凝集素家族中的一員。半乳?凝集素12 主要表現在脂肪組織，且其對於脂肪細胞的分化扮演重要的角色。當在細胞中大?表現時會造成細胞的凋亡。脂肪組織除?儲存能?的功能外也被認為是一個免疫器官會調節身體的代謝和發炎反應，脂肪細胞被認為具有免疫細胞的功能能引發與調節發炎反應。肥胖會造成T 細胞和巨噬細胞浸潤到脂肪組織中並與脂肪細胞交互作用進而分?促發炎反應的激素與趨化因子。脂肪細胞、T 細胞和巨噬細胞共同形成?一個緊密調節的paracrine 迴?，維護並促進脂肪組織中的的炎症反應。本計畫主要是嘗試瞭解半乳?凝集素12 在與脂肪組織相關的發炎反應中所扮演的角色。我們發現T 細胞和巨噬細胞表現半乳?凝集素12。在半乳?凝集素12 缺失的T 細胞會較趨向分化為Th1 而巨噬細胞會分化為抑制發炎反應的M2 巨噬細胞。我們?用基因晶片分析半乳?凝集素12 剔除?鼠的脂肪組織發現許多與發炎反應(e.g. Zap70, Ppp3cc, Cacna1h, Cacna2d1)相關的基因。其中protein kinase C ??與?一個調控發炎反應很重要的訊息傳遞?徑：NF-B 的訊息傳遞 ?徑。我們假設半乳?凝集素 12 剔除會影響脂肪細胞的免疫功能、T 細胞及巨噬細胞的分化，以及調節由NF-B 所調控的發炎反應。這樣的假設將進一步經由以下的具體目標?達成：具體目標 1：探討半乳?凝集素- 12 在脂肪細胞的作用具體目標 2：探討 T 細胞中的半乳?凝集素- 12 的功能和脂肪細胞調控T 細胞分化的影響具體目標 3：探討巨噬細胞中的半乳?凝集素- 12 的功能和脂肪細胞調控巨噬細胞分化的影響本計畫執?結束後，將對半乳?凝集素 12 如何影響發炎反應有所?解。而慢性發炎反應對於許多?同的疾病多有關係，經由進一步瞭解半乳?凝集素12 對於發炎反應的影響將有助於我們發展?好的針對代謝症候群的治?藥物。 Galectin-12 is a member of a family of animal lectins that are defined by their affinity for -galactosides and their consensus amino acid sequences. Galectin-12 contains 2 carbohydrate recognition domains (CRDs) joined by a linker region in a single polypeptide chain. Galectin-12 is predominantly expressed in the adipose tissue, and it plays an important role in adipocyte differentiation and apoptosis promotion when overexpressed in vitro. Adipocytes exhibit immune cell functions, which prime inflammatory responses. During obesity, T-cells and macrophages infiltrate white adipose tissue (WAT), and along with adipocytes, secrete a variety of pro-inflammatory cytokines and chemokines. Adipocytes, T-cells, and macrophages together form a closely regulated paracrine loop, which maintains and promotes the inflammatory response in the adipose tissue. This proposed project aims to characterize the role of galectin-12 in adipose tissue-related chronic inflammation. Our results show that galectin-12 is expressed in T-cells and macrophages. Galectin-12 knockouts demonstrated the polarization of T-cells toward Th1 and the differentiation of macrophages to M2 macrophages. We also performed cDNA microarray analysis and found that the expression of several genes is altered in the adipose tissue from galectin-12-deficient mice. Some of these genes are known to participate in the inflammatory response (e.g., Zap70, Ppp3cc, Cacna1h, Cacna2d1). Moreover, the expression levels of protein kinase C (PKC), which participates in various inflammatory responses via NF-κB signaling, were altered. We hypothesize that galectin-12 knockdown will alter adipocyte immune cell-like function, contribute to T-cell and macrophage differentiation, and modulate the NF-B mediated inflammatory response. This hypothesis will be addressed through the following specific aims: Specific aim 1: To investigate the role of galectin-12 in adipocytes Specific aim 2: To investigate the regulatory function of galectin-12 in T-cells and the role of adipocytes in T-cell polarization Specific aim 3: To investigate the regulatory function of galectin-12 in macrophages and the effect of adipocytes on macrophage differentiation By satisfying these specific aims, we will gain new insights into the significance of galectin-12 in the regulation of chronic inflammation. Chronic inflammation has profound implications for various clinical symptoms and diseases, and therefore, improved knowledge of the effects of galectin-12 will be important for developing treatments for metabolic syndromes.
顯示於類別:	[中醫學系暨碩博班] 研究計畫

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