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標題: | 探討皮膚刺激物誘導毛囊再生的機轉 The mechanism of hair follicle regeneration induced by skin irritation |
作者: | Chun-Kai Lin 林群凱 |
指導教授: | 林頌然(Sung-Jan Lin) |
關鍵字: | 毛囊,毛囊幹細胞,十二烷基硫酸鈉,刺激性接觸性皮膚炎,巨噬細胞,VEGF信號傳導途徑, Hair follicle,Hair follicle stem cells,Sodium dodecyl sulfate,Irritant contact dermatitis,Macrophage,VEGF signaling, |
出版年 : | 2016 |
學位: | 碩士 |
摘要: | 皮膚為人體最大的器官,具有高複雜性與高功能性,也具有許多附屬器官,而毛囊為其中一個重要的附屬器官。毛囊是一個高自主性的微小器官,具有毛囊幹細胞與自我生長週期,型態會隨著生長週期的不同而有所變化。因此,毛囊本身的生理調控,以及在受到外界環境刺激後的生理調控與修復機制,以及與環境之間的溝通與響應,都成為再生醫學研究的範疇,使得毛囊成為再生醫學研究重要的實驗研究模型。
休止期時期的毛囊會受到許多引發因子(initiator)的影響而活化,細胞增生而逐漸生長進入生長期狀態,而這些引發因子的相關研究蓬勃發展。本研究目標希冀能探索毛囊感應到外界刺激後活化,而從休止期狀態生長進入生長期。本研究以十二烷基硫酸鈉(Sodium dodecyl sulfate, SDS)作為皮膚刺激物,並在休止期時期時給予刺激,誘發刺激性接觸性皮膚炎。在SDS連續刺激下,休止期狀態的毛囊,其毛囊幹細胞活化而進行細胞增生,毛囊逐漸生長而過早地進入生長期。在SDS連續刺激後,引發許多免疫細胞浸潤到毛囊周圍區域,包括嗜中性白血球和巨噬細胞。之後,我們將巨噬細胞耗竭,而不是嗜中性白血球耗竭,可以明顯地阻擋SDS刺激後休止期毛囊過早進入生長期,此結果可以得知巨噬細胞在SDS刺激而誘發休止期毛囊活化生長而提早進入生長期中扮演重要角色。 本研究也指出血管內皮生長因子(VEGF)在SDS刺激後,表現量會明顯地增加,且與巨噬細胞有關聯性。抑制VEGF信號傳導途徑可以延遲SDS刺激所誘發休止期毛囊活化生長而提早進入生長期。 總言之,本研究建立一個休止期狀態的毛囊在響應SDS刺激表皮後,活化生長而過早進入生長期的實驗模型,也發現巨噬細胞和VEGF信號傳導途徑可能在其中扮演重要角色。 Skin, the largest organ in a human body, exhibits high structural complexity for its unique functions. Hair follicles, one of the skin appendages, are a miniorgan with distinct lifelong cyclic growth that are fueled by their resident stem cells. The activity of hair follicle stem cells are tightly regulated by their niche microenvironment for physiological growth as well as regeneration after injuries. Therefore, hair follicles provide an excellent model for the research of stem cell biology. The telogen hair follicles, activated by many initiators, undergo cell proliferation and become anagen hair follicles, and the researches of these initiators have become popular and well development recently. This study is aimed at exploring how hair follicles react to irritation to interfollicular epidermis to regenerate from telogen to anagen. We employed the irritant sodium dodecyl sulfate (SDS) to induce irritant contact dermatitis during telogen phase. We found that, after SDS treatment, hair follicle stem cells were activated and hair follicles entered anagen prematurely. This was associated with infiltration of immune cells, including neutrophils and macrophages, in the perifollicular environment. Depletion of macrophages, but not neutrophils, prohibited SDS-induced anagen entry, indicating that activated macrophages are essential for hair follicle stem cell activation by SDS treatment. Molecularly, increased expression of vascular endothelial growth factor (VEGF) was associated with macrophage infiltration. Inhibition of VEGF signaling delayed SDS-induced anagen entry. In summary, this study shows that hair follicles are able to initiate a protective regenerative reaction in the presence of irritation to interfollicular epidermis. Activation of macrophages and VEGF signaling are involved in activating hair follicle stem cells. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50489 |
DOI: | 10.6342/NTU201600968 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學工程學研究所 |
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