探討交感神經提供易活化毛囊幹細胞的環境

Abstract

交感神經突觸會生長進入皮膚並與毛囊和一旁的豎毛肌纏繞形成最簡單的豎 毛單元。透過分泌正腎上腺素，交感神經得以促使毛髮站立來增大動物的體型並 且調控溫度。在毛髮生長週期中，交感神經的纖維會表現出消長的現象，在進入 生長期前期時增加，當進行到中期到後期這段時間開始減少。而在角質細胞中， 正腎上腺素會有抑制細胞分裂並刺激細胞分化的作用。在人體身上使用乙型 2 型 腎上腺素受體抑制劑發現有掉髮的現象，由此暗示交感神經擁有可以影毛髮生理 恆定的能力。 在我們的研究中發現，交感神經跟毛囊突隆區有距離相當近的交集。交感神經纖 維在生長期前期均勻地在整片背皮中分佈，並且有其密度有上升的現象。而在使 用六羥多巴胺除掉交感神經後，毛囊從休止期進入生長期、和生長期前期進入生 長期後期的過程會被阻斷，但是如已經進入生長期後期則沒有影響。使用乙型腎 上腺素受體促進劑(異丙腎上腺素)可以刺激毛髮提前進入生長期。從我們的結 果得知交感神經在自然進入生長期的生長期前期中扮演重要角色。我們更進一步 分離出毛囊幹細胞來探討交感神經移除與不移除對於基因表現的變化。其中 Wnt 信號並不會受到交感神經得去除的影響。然而，Gli1 和 Gli2 的信號在交感神經去 除後很顯著的表現有下降的情況，這很可能是交感神經可以透過刺激生成 hedgehog 信號來活化毛囊幹細胞。但在知道交感神經並不會分泌 Shh 訊號的情況 下，我們認為交感神經可能透過其他方式來調控 hedgehog 在毛囊的表現。

The sympathetic nerve innervates in the skin and associates with hair follicles and arrector pili muscles to assemble the piloerection units. Through secretion norepinephrine, the sympathetic nerves system can trigger piloerection to expand body size and mediate body temperature. During hair cycle, the sympathetic nerve fibers oscillate with hair cycle phase which increases at the early anagen but decreases at the mid-anagen to the regression stage in the hair follicles. Treatment with norepinephrine can inhibit keratinocyte proliferation and trigger cell differentiation. The administration of adrenoceptor antagonist propranolol will lead to hair loss in the human which imply the sympathetic nerves may involve in hair follicle homeostasis regulation. In our study, we identify that the sympathetic nerve closely associates with bulge region of the hair follicle. The neuron fibers density increases and homogeneously distributes in the interfollicular regions of the back skin at the early anagen phase. The 6- hydroxydopamine induced sympathectomy block telogen-to-anagen transition, early anagen I-to-anagen III transition, but not full anagen progression. Beta-adrenoceptor agonist, isoproterenol, can induce an early hair cycle progression. In our result, the sympathetic nerve is important in the early spontaneous hair cycle entry. We further isolate the hair follicle stem/progenitor cells (HFSC) and identify the gene expression profile in sympathectomy and non-sympathectomy skin. The Wnts expression is not affected after sympathectomy. However, the gli1, gli2 significantly decrease in hair follicle stem cells after sympathectomy which indicates that sympathetic nerves can activate HFSC through activating hedgehog signaling. Furthermore, no study showed SN can secrete Shh. Therefore, we conclude that sympathetic nerves can mediate hair cycle through the alternative pathway by mediating the hedgehog pathway.