48小時高糖環境下之臍靜脈內皮細胞基因表現變化

Analysis of gene expression changes in HUVECs under 48-hour high glucose exposure

馬崇獻(Chung-Hsien Ma)

指導教授 ： 翁資雅

元智大學/資訊學院/資訊工程學系/碩士(2013年)

https://doi.org/10.6838/YZU.2013.00288

摘要

糖尿病是一種慢性疾病，於1979年American Diabetes Association將糖尿病分類為第一型糖尿病(type 1 diabetes ,T1D)，第二型糖尿病(type 2 diabetes,T2D)，姙娠期糖尿病(gestational diabetes, GDM)和其他型糖尿病。根據世界衛生組織估計到2030年若沒有有效治療方法，患者人口可能倍增至4億3000萬人。
研究指出糖尿病患者因為細胞長時間處在高血糖環境之下，細胞受到高糖誘導造成血管內皮細胞功能障礙，並且使糖尿病患者產生血管併發症，本篇我們利用臍靜脈內皮細胞 (Human Umbilical Vein Endothelial Cells; HUVECs)，來培養細胞，分別在0小時與24小時餵養在高血糖環境至48小時，主要研究細胞凋亡機制在不同時間點的基因表現量變化。利用R軟體中的limma封包挑出57個候選基因 (candidate gene)，結合PANTHER與BIOGRAPH兩個資料庫從中挑選出與胰島素、糖解、細胞凋亡、發炎反應、免疫系統以及糖尿病具有關聯的pathway，接著分別利用TRANSFAC與miRWalk從5-prime找出被TF調控以及在3-prime端被miRNA所調控的基因，結合調控機制與基因表現量的變化，希望能夠建立出受到時間影響下基因表現量的改變與調控機制的關係，進而了解糖尿病的血管併發症與了解細胞凋亡的機制，找到有效防止細胞死亡的目的。

關鍵字

細胞凋亡 ； 內皮細胞 ； 臍靜脈內皮細胞 ； 基因表現

並列摘要

Diabetes is a chronic disease. In 1979, American Diabetes Association categorized diabetes into four types: type 1 diabetes (T1D), type II diabetes (T2D), gestational diabetes (GDM) and other types of diabetes. According to the World Health Organization, if there is no effective treatment with the diabetes, it is estimated that in 2030 the patient population will be doubled to four hundred and thirty million people.
Previous studies show that under high glucose exposure, cells will undergo apoptosis, inducing dysfunction of vascular endothelial cells. This study used the Human Umbilical Vein Endothelial Cells (HUVECs). The current research is focused on mechanism of changes in gene expression at different time points. Using limma package in R software, 57 differentially expressed candidate genes were identified. Combining PANTHER with BIOGRAPH, it is found that these genes are involved with insulin, glycolysis, apoptosis, inflammation, immune function and diabetes-associated pathways. Then, TRANSFAC and miRWalk were used to search for transcription factor (TF) in the 5-prime and microRNA (miRNA) in the 3-prime region of each candidate gene sequence. By establishing a comprehensive regulatory mechanism underlying high glucose induced gene expression changes, we hope to understand the molecular events associated with endothelial cell apoptosis under hyperglycemia, and develop better prevention against vascular complications in diabetes.

並列關鍵字

T2D ； CDK5 ； STAT3 ； ADM ； microarray ； HUVEC

參考文獻

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