探討毛囊退化期中毛囊結構變化及細胞動態

Abstract

上皮-間質幹細胞的相互作用在形態發生(morphogenesis)過程中扮演重要的腳色，例如哺乳動物中的乳腺和毛囊。毛囊是一個立體微器官並且透過上皮-間質幹細胞的相互作用不斷經歷毛囊生長週期。毛囊自出生經由morphogenesis形成毛囊，經歷退化期、休止期、生長期不斷循環。細胞凋亡有助於毛囊消退；然而，早期退化期的細胞動態及細胞分裂仍尚未明瞭。 本次實驗利用組織學分析、免疫螢光染色及活體實時成像監測說明退化期的毛囊結構及細胞動態。利用蜜蠟除毛促使毛囊一致性地進入生長期，並紀錄除毛後第17~23天基底膜(basement membrane)、毛根鞘纖維(dermal sheath)、外根鞘（ORS）細胞的3D立體結構變化。退化期早期(第16~18天)發現一部份毛根鞘纖維細胞死亡、外根鞘細胞開始向上移動。退化期中期(第19~22天) 發現有大量的外根鞘細胞凋亡、基底膜的不完整性、毛根鞘纖維逐漸縮短並在真皮乳突(dermal papilla)的後方形成萎縮的構造。另外發現在退化的過程中細胞分裂發生頻率遠高於Caspase-3誘導的細胞凋亡。 我的研究結果表明，退化期中期大量Caspase-3誘導的細胞凋亡事件發生在近端上皮鏈中。此外Caspase-3誘導的細胞凋亡事件不是觸發毛囊消退的主要因素。

Epithelial-mesenchymal stem cell interactions are characterized as an important role in several organs during morphogenesis. In mammals, mammary glands and hair follicles (HF) are the mini-organ which cycled involution with epithelial-mesenchymal stem cell interactions. After the HFs morphogenesis, the HFs transform from regression (catagen phase), via the telogen, to the anagen, continuous cycling. Cell death contributes to HF regression; however, what is the cell dynamics in the early phase of regression remains unclear. In this study, I used histological analysis, immunofluorescent staining, and live imaging to clarify the structure and cell dynamics in HF regression. HF entered the anagen phase synchronously by waxing. Also, long-term real-time imaging was used to monitor the behavior and structural changes in epithelial cells during HF regression. I demonstrated the 3D structure changing of the HF dermal sheath (HFDS) and the HF basement membrane (HFBM) during regression (from 17 days to 23 days post-waxing). The HFDS was shown that only wrapped the half down of the HF. During the early stage of regression (from 16 days to 18 days post-waxing), few HFDS cells death and meanwhile the epithelial cells began to move. During mid-catagen (from 19 days to 22 days post-waxing), the HFDS involuted the trailing structure behind the DP and the massive apoptotic events were contributed by ORS cells. Surprisingly, the proliferation events much more than the caspase-3 mediate apoptotic events during HF regression. My result suggests that the massive caspase-3 mediate apoptotic events occurred at the proximal epithelial strand which was the thinnest diameter of the dermal sheath. Furthermore, the Caspase-3 mediate apoptotic events were not the main factor that triggered the HF regression.