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  本文選題：ABCG2 + 氣管干細胞　； 參考：《中國醫(yī)科大學》2006年博士論文

【摘要】：前言 干細胞是指具有無限或較長期的自我更新能力,并能產生至少一種高度分化子代細胞的細胞。按照組織發(fā)生學來源,可將干細胞分為胚胎干細胞和成體干細胞。近年來對成體干細胞的研究越來越受到重視,目前已發(fā)現(xiàn)的成體干細胞有造血干細胞、骨髓間充質干細胞、神經(jīng)干細胞、肌干細胞、角膜干細胞、胰腺干細胞、皮膚干細胞、肝臟干細胞等,并已不同程度地用于臨床治療。但迄今為止國際上對氣管干細胞的研究還很不完善。先前本研究組已成功地在體內外建立了氟脲嘧啶介導的大鼠氣管損傷修復模型,并對氣管干細胞進行了初步的定位和性狀解析。 干細胞具有排出熒光染料Hoechst33342的特性。近年來的研究表明,干細胞的這一特性(即SP表型)與ATP結合盒(ABC)轉運蛋白超家族成員之一的ABCG2(又名乳癌耐藥蛋白1,Bcrp1)的表達有關�，F(xiàn)已證明在多個物種的多種組織來源的SP細胞中檢測到ABCG2的高表達,如骨髓、肝、肌組織、乳腺上皮及ES細胞。ABCG2與SP表型的密切關系,使得ABCG2成為多潛能干細胞的共同標志,對干細胞的鑒定具有重要意義。為更深入地了解氣管干細胞的特性,本研究在5-FU介導的氣管上皮損傷修復模型的基礎上,應用間接免疫熒光法和Wetern blot動態(tài)觀測了修復過程中各時間點氣管上皮ABCG2蛋白的表達,借以原位觀察了氣管干細胞在整個修復過程中的動態(tài)分布。 近年來的研究表明Wnt信號及其成員對胚胎及成體的原始細胞的增殖和分化具有重要的調節(jié)作用。為探討氣管干細胞的增殖分化與Wnt/β-catenin信號途徑的關系,闡明干細胞增殖分化的分子機制,本研究應用RT-PCR及間接免疫熒光的方法動態(tài)觀測了修復過程中Wnt信號相關成分Wnt1、β-catenin、cyclinD1 mRNA的變化以及β-catenin蛋白的細胞內分布,初步探討了Wnt/β-catenin信號途徑參與調控氣管干細胞增殖
[Abstract]:Preface Stem cells are cells that have unlimited or long-term self-renewal and produce at least one highly differentiated progeny. Stem cells can be divided into embryonic stem cells and adult stem cells according to the origin of histogenesis. In recent years, more and more attention has been paid to the research of adult stem cells. At present, the adult stem cells have been found to be hematopoietic stem cells, bone marrow mesenchymal stem cells, neural stem cells, muscle stem cells, corneal stem cells, pancreatic stem cells, skin stem cells. Liver stem cells and so on, and have been used in clinical treatment to varying degrees. However, the international research on tracheal stem cells is not perfect. The model of rat trachea injury induced by fluorouracil in vitro and in vivo has been successfully established, and the primary localization and character analysis of tracheal stem cells have been carried out. Stem cells are characterized by the emission of fluorescent dye Hoechst33342. Recent studies have shown that this characteristic of stem cells (SP phenotype) is related to the expression of ABCG2 (also known as Bcrp1), a member of the ATP binding cassette transporter superfamily. It has been proved that high expression of ABCG2 has been detected in SP cells from many species, such as bone marrow, liver, muscle, mammary epithelium and es cells. ABCG2 is closely related to SP phenotype, which makes ABCG2 a common marker of multipotential stem cells. It is of great significance for the identification of stem cells. In order to better understand the characteristics of tracheal stem cells, the expression of ABCG2 protein in tracheal epithelium at different time points was dynamically observed by indirect immunofluorescence and Wetern blot on the basis of 5-FU mediated repair model of tracheal epithelial injury. The dynamic distribution of tracheal stem cells during the whole repair process was observed in situ. Recent studies have shown that Wnt signaling and its members play an important role in regulating the proliferation and differentiation of embryonic and adult primordial cells. To investigate the relationship between proliferation and differentiation of tracheal stem cells and Wnt/ 尾 -catenin signaling pathway, and to elucidate the molecular mechanism of stem cell proliferation and differentiation. In this study, RT-PCR and indirect immunofluorescence were used to dynamically observe the changes of Wnt signal related components Wnt1, 尾 -catenin D1 mRNA and the intracellular distribution of 尾 -catenin protein, and to explore the role of Wnt/ 尾 -catenin signaling pathway in regulating the proliferation of tracheal stem cells.
【學位授予單位】：中國醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R329

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本文編號：1859161