microRNAs 在牙齦增生之調控角色研究

The Study of the Role of microRNAs in the Regulation Gingival Overgrowth

邱美芳(Mei-Fang Chiu)

指導教授 ： 林泰元

國立臺灣大學/醫學院/藥理學研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.00721

摘要

長期服用抗癲癇藥物phenytoin而造成藥物誘發牙齦增生個案於最早於1939年被報導。隨後，免疫抑制劑cyclosporin A和鈣離子阻斷劑nifedipine也被發現會造成牙齦增生。藥物誘發牙齦增生的發生率隨不同藥物而有所不同。大約百分之五十的患者服用phenytoin會造成牙齦增生；使用cyclosporin A和nifedipine而產生這種副作用的比例分別是百分之三十和百分之二十。牙齦增生在病理組織上的改變主要是纖維化或增大的結締組織和增厚的上皮。目前為止，大部分的研究結果指出在結締組織細胞外間質特別是膠原蛋白的堆積在牙齦增生的過程中扮演重要的角色。然而，在牙齦增生中造成上皮細胞增生的機轉仍未明。在這個研究中，我們發現p63這個維持上皮幹細胞的必須因子在先天性和藥物誘發牙齦增生的上皮組織中有過度表現的現象。再者，透過microarray的分析，發現先天性和藥物誘發的牙齦增生組織中有些microRNA (miRNA) 與在正常牙齦組織中表現不同。這些miRNA可能透過作用在p63上而調控角質幹細胞。miRNAs被認為會調控細胞生長、分化、及死亡，而根據這個研究顯示服用藥物而造成牙齦增生的這個副作用可能是透過miRNA調控角質幹細胞而來的。

關鍵字

微核糖核酸 ； 牙齦增生 ； 角質幹細胞

並列摘要

Drug-induced gingival overgrowth was first reported in 1939 as a consequence of chronic usage of anti-epileptic drug phenytoin. Later, immunosuppressive drug cyclosporin A and calcium channel blocker nifedipine were observed to cause gingival overgrowth, too. The incidence of gingival overgrowth caused by these three drugs are not the same. Approximately 50 % of patients taking phenytoin are facing with this disturbing side effect while 30 % and 20 % for patients taking cyclosporin A and nifedipine, respectively. Histological change of gingival overgrowth is characterized by fibrotic or expanded connective tissues as well as an enlarged gingival epithelium. So far, many reports have indicated that extracellular matrix accumulation in connective tissue, particularly the collagenous component, played the important roles in gingival overgrowth. However, the pathogenic mechanisms for epithelial cells hyperproliferation of gingival overgrowth were largely unknown. In our recently study, we found that p63, the essential factors for epithelial stem cell maintenance, was overexpressed in epithelium of inherited and phenytoin-induced gingival overgrowth tissue compared with normal gingival tissue. Furthermore, the analysis for microRNA expression profiles of inherited and drug-induced gingival overgrowth by microRNA arrays and real-time PCR indicated that some microRNAs expressed differently between gingival overgrowth tissue and normal gingival tissue. And, these microRNAs might target to p63 and regulate keratinocytes stem cell stemness. It have been reported that microRNAs were well known to regulate cell proliferation, differentiation, and cell death, therefore, our findings suggested that the unwanted side effect of these drugs might be caused through the regulation between microRNAs and keratinocyte stem cell.

並列關鍵字

microRNA ； gingival overgrowth ； keratinocyte stem cell

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