https://scholars.lib.ntu.edu.tw/handle/123456789/202031
Title: | 原發性肺纖維化病人基因表現與多型性之分析 | Authors: | ���R�R | Issue Date: | 31-Jul-2004 | Publisher: | 臺北市:國立臺灣大學醫學院檢驗醫學科 | Abstract: | 原發性肺纖維化(IPF)是原因不明的間質性肺疾, 其特徵是肺泡組織因細胞凋 亡而破壞, 纖維細胞增生, 以及膠原蛋白之大量沉積.對原發性肺纖維化的研 究常以bleomycin 在小白鼠引發肺組織纖維化作為動物模式, Kaminski 等人利 用oligonucleotide microarrays 研究小白鼠之肺臟對於bleomycin 所反應出 之基因表現, 因而發現有一組基因之表現與纖維化有關, 其中表現最強的基因 之一是osteopontin. Osteopotin 是一種含有arginine-glycine-asparatic acid (RGD) 的蛋白質, 很多細胞都會分泌 osteopontin, 包括osteoclasts, activated T cells, 以 及 activated macrophages. osteopontin 基因會進行alternative RNA splicing, 產生三種不同的cDNA, 這些splice variants 的功能尚不清楚. 在本計劃中我們研究原發性肺纖維化病人, 以及其他可能導致肺纖維化之疾病 如急性間質性肺炎,肺泡蛋白沉著症之病人, 其osteopontin mRNA 之表現, 以 RT-PCR 及direct sequencing 方法, 研究病人周邊血液單核血球所表現之 osteopontin mRNA. 我們發現, osteopontin mRNA 之一種splice variant (缺 乏exon 5),可能與原發性肺纖維化之嚴重程度及預後有關, 但與肺泡蛋白沉著 症之嚴重程度及預後無關. 目前我們仍在繼續收集更多病例. Idiopathic pulmonary fibrosis (IPF), is an interstitial lung disease of unknown cause, characterized by the loss of alveolar architecture through the apoptosis of epithelial and endothelial cells, proliferation of myofibroblasts , and extensive deposition of extracellular matrix proteins, especially collagens type I and III. The molecular basis of pulmonary fibrosis has been studied in a murine model. In mouse with pulmonary fibrosis induced by bleomycin, the expression of a large cluster of genes were augmented, and osteopontin was one of these most dramatically induced genes. Osteopontin is an arginine-glycine-asparatic acid (RGD)-containing protein secreted by a variety of cells, including osteoclasts, activated T cells, and activated macrophages. There is evidence of alternative RNA splicing of the osteopontin gene with three osteopontin cDNAs identified. The function of these splice variants is unknown. In the present study we examined the mRNA expression of osteopontin gene in patients with idiopathic interstitial fibrosis IPF), acute interstitial pneumonitis (AIP) and idiopathic pulmonary alveolar proteinosis (PAP), by RT-PCR and direct sequencing of osteopontin mRNA transcripts. We found that the expression of a splice variant mRNA of osteopontin gene, which lacks exon 5, is associated with severity and poor prognosis of IPF, but not with prognosis of PAP. We are currently continuing to collect more cases of idiopathic pulmonary fibrosis and other interstitial lung disease which ends up with fibrosis, and examine the mRNA expression of osteopontin gene, including its variant forms caused by alternative splicing. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/27346 | Other Identifiers: | 922314B002304 | Rights: | 國立臺灣大學醫學院檢驗醫學科 |
Appears in Collections: | 醫學系 |
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