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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳金洌(Jen-Leih Wu) | |
| dc.contributor.author | Keng-Yu Chiang | en |
| dc.contributor.author | 江耕宇 | zh_TW |
| dc.date.accessioned | 2022-11-23T08:58:21Z | - |
| dc.date.available | 2021-11-03 | |
| dc.date.available | 2022-11-23T08:58:21Z | - |
| dc.date.copyright | 2021-11-03 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-28 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79335 | - |
| dc.description.abstract | 肝臟是人體必需的最大器官。當肝臟受到病原體、毒素、自身免疫性疾病、部分肝切除術或肝癌的損害時，它具有快速有效的修復能力。除了肝臟再生，抗發炎過程對於肝臟修復也很重要。在本論文中，我們分別利用斑馬魚及吳郭魚動物模式探討肝臟再生和免疫反應之機制。論文的前半部講述我們利用肝臟專一性表達螢光基因斑馬魚建立部分肝切除再生模式。我們發現在部分肝切除後，腹腔注射活體型反義寡核苷酸會抑制顆粒蛋白前體A型表現並延遲肝再生。此外，轉錄體學分析和即時聚合酶鏈鎖反應結果顯示比較對照組後抑制顆粒蛋白前體A型在部分肝切除三十六小時後可能藉由抑制肝細胞生長因子訊息傳遞路徑使細胞週期和細胞增生不活化。此外，肝臟專一性大量表現顆粒蛋白前體A型轉基因斑馬魚在部分肝切除後會促進細胞增生。因此，我們認為顆粒蛋白前體A型可以正向調節肝細胞生長因子訊息傳遞路徑以促進肝臟再生機制中的肝臟細胞增生。論文的後半部講述我們建立了具有單一或雙重表現鮭魚delta-5脂肪酸去飽和酶和delta-6脂肪酸去飽和酶之轉基因吳郭魚，接著利用創傷弧菌進行細菌感染。以亞麻籽油配方餵食的肝臟和肌肉專一性單一或雙重表現delta-5脂肪酸去飽和酶和delta-6脂肪酸去飽和酶轉基因吳郭魚均顯示N-3多元不飽和脂肪酸含量更高。其中，N-3多元不飽和脂肪酸含量高的雙重表達轉基因吳郭魚在創傷弧菌感染後存活率提高及抑制發炎和免疫相關基因表現。腸道微生物組分析進一步顯示雙重表達轉基因吳郭魚具有較高的腸道微生物群多樣性，而發炎相關微生物群中的普雷沃氏菌科較低。因此，我們的研究結果顯示雙重表現鮭魚delta-5脂肪酸去飽和酶和delta-6脂肪酸去飽和酶轉基因吳郭魚增強抗病力可能與N-3多元不飽和脂肪酸含量增加和腸道微生物群組成改變有關。總結上述，本論文提出了抗發炎生長因子顆粒蛋白前體及N-3多元不飽和脂肪酸分別對於當肝臟受損時促進肝細胞增殖和提高對病原體的抗發炎作用的有正向調節之作用。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-23T08:58:21Z (GMT). No. of bitstreams: 1 U0001-2710202102574500.pdf: 36456531 bytes, checksum: 4ad0270779b68ff56ba9309090609919 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 論文口試委員審定書 I 謝辭 II 摘要 III Abstract V Table of Contents VII List of Figures XI List of Tables XIII 1. Introduction 1 1.1 Liver 1 1.2 Liver embryonic development and regeneration 1 1.3 Liver regeneration 2 1.4 Pending issue of liver regeneration 2 1.5 HGF/c-Met signaling in liver regeneration 3 1.6 Progranulin in hepatic growth 4 1.7 The elusive regulatory role of progranulin in liver regeneration 4 1.8 Liver damage caused by pathogens infection 5 1.9 Biosynthesis of omega-3 polyunsaturated fatty acids 6 1.10 N-3 PUFAs and immune responses 7 1. 11 N-3 PUFAs and gut microbiota 7 1. 12 Prospection of n-3 PUFAs enriched tilapia against infection by pathogens 8 2. Materials and Methods 10 2.1 Fish 10 2.2 Establishment of transgenic fish 11 2.3 Morpholino design and Intraperitoneal injection 12 2.4 Partial Hepatectomy 13 2.5 RNA Sequencing and Analysis 13 2.6 Cell cycle analysis by flow cytometry 14 2.7 Quantitative real-time PCR 15 2.8 Western blots and Immunohistochemistry 16 2.9 Imaging 17 2.10 Fatty acid extraction and analysis 17 2.11 Vibrio vulnificus culture 18 2.12 Vibrio vulnificus challenge 18 2.13 DNA extraction and sequencing of gut microbiota 19 2.14 Statistical analysis 20 3. Results 21 3.1 Section I: The regulatory role of progranulin involved in liver regeneration after partial hepatectomy 21 3.1.1 Zebrafish progranulin A is involved in liver regeneration of hepatectomized zebrafish 21 3.1.2 Knockdown of GrnA delays liver regeneration after partial hepatectomy 22 3.1.3 Transcriptome analysis 24 3.1.4 GrnA morphants exhibit impaired liver regeneration with suppressed cell cycle and cell proliferation 26 3.1.5 Knockdown of GrnA prevents signaling through the HGF/c-met axis after partial hepatectomy 28 3.1.6 Liver-specific expression of GrnA in transgenic zebrafish promotes hepatocyte proliferation after partial hepatectomy 29 3.2 Section II: Dual expression of transgenic delta-5 and delta-6 desaturase in tilapia enhances resistance to Vibrio vulnificus infection 31 3.2.1 Tissue-specific expression of desaturases in tilapia 31 3.2.2 Fatty acid compositions of basal diet and supplemented linseed oil 33 3.2.3 LO basal diet increased the DHA content in dual-transgenic tilapia 33 3.2.4 Dual-transgenic tilapia had improved survival after Vibrio vulnificus challenge 34 3.2.5 Inflammatory gene expression after Vibrio vulnificus infection was attenuated in transgenic tilapia 36 3.2.6 High bacterial diversity and decrease of inflammation-associated gut microbiota in transgenic tilapia 38 4. Discussion 40 4.1 Section I: The regulatory role of progranulin involved in liver regeneration after partial hepatectomy 40 4.2 Section II: Dual expression of transgenic delta-5 and delta-6 desaturase in tilapia enhances resistance to Vibrio vulnificus infection 45 References 50 Figures 68 Tables 96 Appendix 98 | |
| dc.language.iso | en | |
| dc.title | 魚類肝臟的再生及免疫反應之分子調控機制 | zh_TW |
| dc.title | Fish Liver Molecular Functions Involved in Regeneration and Immune Responses | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 洪健睿(Hsin-Tsai Liu),陳志毅(Chih-Yang Tseng),龔紘毅,呂明偉,耿全福 | |
| dc.subject.keyword | 顆粒蛋白前體,部分肝切除手術,肝細胞生長因子,肝臟再生,脂肪酸去飽和酶,多元不飽和脂肪酸,普雷沃氏菌科, | zh_TW |
| dc.subject.keyword | Progranulin,Partial hepatectomy,Hepatocyte growth factor,Liver regeneration,Desaturase,Omega-3 polyunsaturated fatty acids,Prevotellaceae, | en |
| dc.relation.page | 134 | |
| dc.identifier.doi | 10.6342/NTU202104295 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-10-28 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生命科學系 | zh_TW |
| 顯示於系所單位： | 生命科學系 | |
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