本文選題：表皮干細(xì)胞　切入點(diǎn)：P物質(zhì)　出處：《第三軍醫(yī)大學(xué)》2006年博士論文

【摘要】：表皮干細(xì)胞(Epidermal Stem Cells，ESC)是皮膚發(fā)育、代謝以及損傷修復(fù)的重要細(xì)胞源泉，它不僅決定了表皮的形成和代謝，同時參與了毛囊的形態(tài)發(fā)生、生理周期的維持，以及損傷毛囊的修復(fù)。探討ESC分化機(jī)制有助于尋找提高皮膚愈合速度與質(zhì)量的措施，促進(jìn)創(chuàng)傷愈合、提高創(chuàng)傷愈合質(zhì)量。 以往研究證實(shí)，ESC中的β-catenin是啟動ESC分化進(jìn)程與分化方向的關(guān)鍵蛋白。β-catenin是Wnt信號通路一種重要的胞內(nèi)糖蛋白，低水平β-catenin是ESC保持干細(xì)胞狀態(tài)的必要條件之一，當(dāng)其表達(dá)上調(diào)后，ESC進(jìn)入分化進(jìn)程，β-catenin高水平表達(dá)的ESC向毛囊方向分化，若去除β-catenin則向表皮細(xì)胞方向分化。了解調(diào)控β-catenin表達(dá)的機(jī)制對探討主導(dǎo)ESC的分化方向，促進(jìn)毛囊的修復(fù)與重建的措施，以及開展皮膚組織工程中的毛囊重建均有重要意義。 感覺神經(jīng)肽P物質(zhì)(substance p，SP)作為一種研究多年的細(xì)胞因子，以往對于它的研究主要集中于作為神經(jīng)遞質(zhì)、激素和調(diào)質(zhì)發(fā)揮的作用。創(chuàng)傷時不僅感覺神經(jīng)末梢釋放SP，同時在組織修復(fù)過程中，成纖維細(xì)胞、內(nèi)皮細(xì)胞等修復(fù)細(xì)胞在神經(jīng)末梢釋放的SP的誘導(dǎo)下，上調(diào)SP基因及蛋白的表達(dá)，作為自分泌信號促進(jìn)成纖維細(xì)胞、內(nèi)皮細(xì)胞的增殖，并誘導(dǎo)多種參與愈合的其他細(xì)胞因子及蛋白(EGF、bFGF、β-catenin、VEGF、MMPs、NF-κB和fibronectin等)表達(dá)上調(diào)。 尤其值得注意的是，本課題組前期研究發(fā)現(xiàn)，SP是誘導(dǎo)ESC分化和遷移的重要細(xì)胞因子。臨床研究也注意到，，SP與ESC參與構(gòu)建的毛囊的形態(tài)發(fā)育關(guān)系密切。皮膚注射SP可以誘導(dǎo)萎縮的毛囊再生；耗竭成鼠SP，毛囊會萎縮并消失�；赟P和β-catenin在ESC分化方向調(diào)控中的作用，提示SP可能通過調(diào)控β-catenin表達(dá)實(shí)現(xiàn)細(xì)胞外信號到細(xì)胞內(nèi)信號的轉(zhuǎn)導(dǎo)，進(jìn)而調(diào)控ESC分化方向。CK1ε是β-catenin上游調(diào)控蛋白，與Wnt信號通路的GSK3協(xié)同控制β-catenin的Sr45的磷酸化，從而調(diào)控β-catenin表達(dá)：SP與特異性受體NK-R結(jié)合，水解4，5-二磷酸磷脂酰肌醇(PIP_2)生成1，4，5-三磷酸肌醇(IP_3)和二�；视�(DG)雙信使，而PIP_2對CK1ε表達(dá)具有負(fù)向調(diào)節(jié)作用�；谝陨弦罁�(jù)，我們推論：1．SP通過調(diào)節(jié)β-catenin表達(dá)實(shí)現(xiàn)對ESC分化的調(diào)控；2)．
[Abstract]:Epidermal Stem cells ESCs are important cell sources for skin development, metabolism and damage repair. They not only determine the formation and metabolism of epidermis, but also participate in the morphogenesis of hair follicles and the maintenance of physiological cycle. To explore the mechanism of ESC differentiation is helpful to find ways to improve the speed and quality of skin healing, promote wound healing and improve the quality of wound healing. Previous studies have confirmed that 尾 -catenin is the key protein to initiate the differentiation and differentiation of ESC. 尾 -catenin is an important intracellular glycoprotein in Wnt signaling pathway, and 尾 -catenin is one of the necessary conditions for ESC to maintain stem cell status. When the expression of 尾 -catenin entered the differentiation process, the ESC expressed in high level of 尾 -catenin differentiated to the hair follicle, and if the 尾 -catenin was removed, it differentiated to the epidermal cells. Understanding the mechanism of regulating the expression of 尾 -catenin was helpful to explore the differentiation direction of the dominant ESC. It is of great significance to promote the restoration and reconstruction of hair follicles and to carry out the reconstruction of hair follicles in skin tissue engineering. Sensory neuropeptide substance substance (SP) is a cytokine that has been studied for many years. In the past, it was mainly studied as a neurotransmitter. During the process of tissue repair, the expression of SP gene and protein was up-regulated by fibroblasts, endothelial cells and other repair cells induced by SP released from nerve endings. As an autocrine signal, endothelial cells proliferate and induce the up-regulation of the expression of many other cytokines and proteins involved in healing, such as EGF- 魏 B and fibronectin. It is particularly noteworthy that, Our previous study found that SP is an important cytokine to induce differentiation and migration of ESC. Clinical studies also noted that SP is closely related to the morphological development of hair follicles constructed by ESC. Skin injection of SP can induce hair follicle regeneration in atrophy. According to the role of SP and 尾 -catenin in the regulation of differentiation direction of ESC, SP may realize the transduction of extracellular signal to intracellular signal by regulating the expression of 尾 -catenin. Furthermore, CK1 蔚 regulates the differentiation direction of ESC. CK1 蔚 is a 尾 -catenin upstream regulatory protein, which co-controls the phosphorylation of 尾 -catenin Sr45 with the GSK3 of Wnt signaling pathway, and thus regulates the expression of 尾 -catenin to bind to the specific receptor NK-R. Hydrolyzed PIP _ 2) to produce a double messenger of 1 / 4 / 5-inositol triphosphate (IP3) and diacylglycerol (DG), while PIP_2 has a negative effect on the expression of CK1 蔚. Based on the above, we infer that 1.SP regulates the differentiation of ESC by regulating 尾 -catenin expression.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R329

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 蘇小虎;SP對內(nèi)蒙古絨山羊皮膚干細(xì)胞β-catenin及BMP2/4表達(dá)影響的初步研究[D];內(nèi)蒙古農(nóng)業(yè)大學(xué);2012年

本文編號：1657466