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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李士傑(Shyh-Jye Lee) | |
| dc.contributor.author | Wei-Lin Hsu | en |
| dc.contributor.author | 許維麟 | zh_TW |
| dc.date.accessioned | 2022-11-25T03:06:29Z | - |
| dc.date.available | 2026-09-30 | |
| dc.date.copyright | 2021-10-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-04 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81913 | - |
| dc.description.abstract | "組織修復和再生對於生物體的生存至關重要。哺乳動物再生能力的缺失，使得斑馬魚等保留強大再生能力的動物成為研究再生調節機制的珍貴模式。巨噬細胞對損傷反應非常重要，近期的研究更發現它們會參與組織修復和再生，而其調節機制仍然未明。在斑馬魚中，側線系統是快速再生的器官之一，且其位於體表易於觀察。側線的感覺器官是神經丘(neuromast)，以神經丘間細胞(interneuromast cells)相連。此等神經丘間細胞通常被位於下方的許旺氏細胞(Schwann cells)及側線神經(lateral line nerve)抑制而無法分化。目前已知道可以通過抑制許旺氏細胞以活化神經丘間細胞分化為神經丘，但神經丘間細胞是如何脫離許旺氏細胞的抑制仍然未知。為了回答這個問題，實驗室的前成員林孟儒博士以甲硝唑(metronidazole)處理側線特異性表達硝基還原酶(nitroreductase)的轉基因斑馬魚以專一性殺死神經丘，而此方法應不會干擾側線下方之神經與許旺氏細胞的抑制作用。然而他意外的觀察到仍有不到5%的個體再生了神經丘。此外，更發現巨噬細胞會在受損的神經丘周圍巡邏並穿梭於側線神經丘間細胞與下方神經及許旺氏細胞之間，且這少數的再生在巨噬細胞抑制劑的處理下顯著減少。因此，林孟儒博士假設巨噬細胞可能會介入神經丘間細胞和許旺氏細胞之間的空間並打破神經丘間細胞的休眠狀態(quiescence)以促使神經丘的再生。而在此狀態下由於其再生的比例過低，他並沒有發現任一巨噬細胞介入神經丘間細胞與下方神經及許旺氏細胞之間的，爾後再生神經丘的個體。為了克服這個困難，我原計劃使用刺激發炎藥物poly(I:C)來增強斑馬魚巨噬細胞的活性，然而不管是靜脈注射或浸泡方式都無增強效果。因此我改用具有高再生比例的鰭截肢方法來進行進一步的研究。結果顯示，超過一半鰭截肢的個體在截肢後 4 天內可以再生出新的神經丘，並且在抑制巨噬細胞和乙型轉化生長因子(transforming growth factor beta, TGF-β)時顯著的延遲了神經丘的再生。此外，抑制白血球介素-6 (interleukin-6, IL-6)、腫瘤壞死因子-α (tumor necrosis factor alpha, TNFα) 和基質金屬蛋白酶 (matrix metalloproteinases, MMP) 對於再生僅有輕微影響。總體而言，此研究證明巨噬細胞可能會藉由TGF-β訊息傳遞的方式活化神經丘間細胞以再生神經丘。而巨噬細胞介入神經丘間細胞與下方神經及許旺氏細胞之間的個體是否會再生神經丘因技術上的問題則有待進一步研究。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T03:06:29Z (GMT). No. of bitstreams: 1 U0001-3009202114483200.pdf: 6914169 bytes, checksum: a2fffae009b36f34a8c509c88255eba6 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | Table of Contents 口試委員會審定書 i 致謝 ii 中文摘要 iv Abstract vi Table of Contents viii List of Abbreviations xiii Introduction 1 Materials and Methods 7 Zebrafish maintenance and strains 7 Image and microscopy 8 Fin-amputation 8 NTR/Metronidazole-mediated neuromast ablation 8 Liposome injection for macrophage ablation 9 Poly(I:C) injection 9 Immunohistochemistry 10 Rhodamine 123 labeling 11 Pharmacological inhibition 11 Statistical analysis 12 Results 13 Intravenous injection of poly(I:C) fails to enhance macrophage infiltration upon fin amputation 13 Macrophage is the main leukocyte participating in neuromast regeneration post fin amputation 14 Macrophages engage in neuromast regeneration by facilitating the proliferation of progenitor cells 17 Effects of cytokine inhibitors on neuromast regeneration 20 Discussion 24 References 32 Tables 44 Figure 52 Supplementary Figures 65 List of Tables Table 1. Chi-Square analysis of the change of neuromast regeneration by inhibiting macrophages (χ2 values). 44 Table 2. Chi-Square analysis of the change of neuromast regeneration by inhibiting macrophages(p values). 45 Table 3. Chi-Square analysis of the change of neuromast regeneration under LMT-28 treatment (χ2 values). 46 Table 4. Chi-Square analysis of the change of neuromast regeneration under LMT-28 treatment (p value). 47 Table 5. Chi-Square analysis of the change of neuromast regeneration under GM6001 treatment (χ2 values). 48 Table 6. Chi-Square analysis of the change of neuromast regeneration under GM6001 treatment (p value). 49 Table 7. Chi-Square analysis of the change of neuromast regeneration under SB431542 treatment (χ2 values). 50 Table 8. Chi-Square analysis of the change of neuromast regeneration under SB431542 treatment (p value). 51 List of Figures Figure 1. Neuromast regeneration in lateral line of fin-amputated larval zebrafish. 52 Figure 2. Macrophage ablation retards the regeneration of neuromast. 53 Figure 3. Neuromast regeneration is not affected by inhibiting neutrophil recruitment. 55 Figure 4. Inhibition of macrophage reduces cell proliferation in lateral line. 56 Figure 5. Inhibition of macrophages shows no significant effect on the differentiation of regenerated neuromast. 58 Figure 6. Neuromast formation is promoted by inhibiting IL-6 signaling. 60 Figure 7. Neuromast formation is accelerated when inhibiting GM6001. 61 Figure 8. Neuromast progenitor cell proliferation is decreased by inhibiting TGF-β signaling. 62 Figure 9. Neuromast regeneration is not affected by inhibiting TNF- α signaling. 64 List of Supplementary Figures Figure S1. Chemical-genetic ablated neuromasts cannot regenerated with a few exceptions. 65 Figure S2. Macrophages patrol around ablated neuromasts during regeneration. 66 Figure S3. Macrophages were found in between interneuromast cells and Schwann cells during regeneration. 67 Figure S4. Poly(I:C) induces neutrophil recruitment to the yolk. 68 Figure S5. Poly(I:C) induces macrophage recruitment to the yolk. 69 Figure S6. Intravenous injection of poly(I:C) fails to enhance macrophage infiltration upon fin amputation. 70 Figure S7. Clodrosome effectively abolishes the recruitment of macrophages to the tail region. 71 Figure S8. Diclofenac sodium effectively abolishes neutrophil recruitment to the wound site. 72 | |
| dc.language.iso | en | |
| dc.subject | 巨噬細胞 | zh_TW |
| dc.subject | 再生 | zh_TW |
| dc.subject | 側線 | zh_TW |
| dc.subject | 神經丘間細胞 | zh_TW |
| dc.subject | 乙型轉化生長因子 | zh_TW |
| dc.subject | TGF-β | en |
| dc.subject | Macrophage | en |
| dc.subject | regeneration | en |
| dc.subject | lateral line | en |
| dc.subject | interneuromast cell | en |
| dc.title | 巨噬細胞藉由TGF-β增強斑馬魚的神經丘間細胞介導之側線神經丘再生 | zh_TW |
| dc.title | Macrophage enhances interneuromast cell-derived regeneration of lateral line neuromast via TGF-β in zebrafish | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林孟儒(Hsin-Tsai Liu),吳長益(Chih-Yang Tseng),陳振輝,賴時磊 | |
| dc.subject.keyword | 巨噬細胞,再生,側線,神經丘間細胞,乙型轉化生長因子, | zh_TW |
| dc.subject.keyword | Macrophage,regeneration,lateral line,interneuromast cell,TGF-β, | en |
| dc.relation.page | 72 | |
| dc.identifier.doi | 10.6342/NTU202103471 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-10-05 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生命科學系 | zh_TW |
| dc.date.embargo-lift | 2026-09-30 | - |
| 顯示於系所單位： | 生命科學系 | |
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