Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center,
Front Biosci (Landmark Ed). 2016 Jan 1;21(4):856-72. doi: 10.2741/4424.
Carom is a novel protein that regulates membrane curvature and transmits pathophysiological signaling. The tissue expression of Carom is unclear and its functional role and signaling are unknown. We employed a group of combined database mining strategies and established a working model of Carom signaling. We identified 26 Carom partners and established their expression profiles in human and mouse tissues. We classified three tiers of tissues for Carom/partner expression and found lymph node was the tier 1 tissue expressing Carom and most of its partners. Using GEO database, we discovered that four conditions (hypoxia, endometriosis, PPARgamma deletion and iPSC reprogramming) altered Carom/partner expression in endothelial cells. We identified 26 Carom partner signalings by Ingenuity pathway analysis. Ten of the 26 pathways and three genes (ITSN1, UBC and HSPA5) were reported to be regulated in the above four conditions. Paired induction of Carom/ITSN1 elevation was associated with pathological angiogenesis. Whereas, paired reduction of Carom/HSPA5 or UBC was associated with iPSC generation. These results provide an insight on identifying Carom complex model and predicting its functional implications.
钙粘蛋白是一种新型的蛋白,能够调节细胞膜曲率并传递病理生理学信号。钙粘蛋白在组织中的表达尚不清楚,其功能作用和信号通路也不明确。我们采用了一系列组合数据库挖掘策略,建立了钙粘蛋白信号通路的工作模型。我们鉴定了 26 个钙粘蛋白的相互作用蛋白,并建立了它们在人和小鼠组织中的表达谱。我们将组织分为三个层次来表达钙粘蛋白及其相互作用蛋白,发现淋巴结是表达钙粘蛋白及其大部分相互作用蛋白的第一层次组织。利用 GEO 数据库,我们发现四种条件(缺氧、子宫内膜异位症、PPARγ 缺失和 iPSC 重编程)改变了内皮细胞中钙粘蛋白/相互作用蛋白的表达。通过 Ingenuity 通路分析,我们鉴定了 26 种钙粘蛋白相互作用蛋白信号通路。其中 10 条通路和三个基因(ITSN1、UBC 和 HSPA5)在上述四种条件下被报道受到调控。钙粘蛋白/ITSN1 水平的协同升高与病理性血管生成有关,而钙粘蛋白/HSPA5 或 UBC 的协同降低与 iPSC 的生成有关。这些结果为鉴定钙粘蛋白复合物模型和预测其功能意义提供了新的思路。