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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 俞松良 | zh_TW |
| dc.contributor.advisor | Sung-Liang Yu | en |
| dc.contributor.author | 王恩瑋 | zh_TW |
| dc.contributor.author | En-Wei Wang | en |
| dc.date.accessioned | 2021-07-11T15:34:41Z | - |
| dc.date.available | 2024-02-28 | - |
| dc.date.copyright | 2018-10-11 | - |
| dc.date.issued | 2018 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | References
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78990 | - |
| dc.description.abstract | 微核醣核酸(microRNAs)是21-24nt長度的non-coding RNA，可以調節其他基因的表現。研究指出當病原菌感染宿主時，宿主微核醣核酸可以調控發炎或產生抗病原菌感染的免疫反應來抵禦病原菌。因此微核醣核酸在宿主防禦病原菌上有著重要的角色。沙門氏菌(Salmonella)是革蘭氏陰性菌且可生長於宿主細胞內。沙門氏菌可感染吞噬細胞與非吞噬細胞，當沙門氏菌存活於非吞噬細胞內則可再感染鄰近之細胞，若存活於吞噬細胞內可透過血液或淋巴擴散於全身而造成全身性的感染。然而胞內菌在感染宿主腸道上皮細胞時，宿主微核醣核酸的表現或調控關係仍然未知。
實驗使用人類腸道癌症上皮細胞(HT29)感染鼠傷寒沙門氏菌(Salmonella typhimurium)來探討宿主微核醣核酸之表現與病原菌之關係。利用TLDA array分析在沙門氏菌感染後4小時，宿主微核醣核酸之表現量。TLDA分析後發現宿主細胞之miR-146a在沙門氏菌感後其表現量會增加。為了進一步研究宿主miR-146a在沙門氏菌感染時所扮演的角色，使用miR-146a過表現的細胞株(HT29與HIEC，人類腸道正常上皮細胞)感染沙門氏菌並且觀察其細胞內細菌生長(intracellular growth)之情形。實驗結果顯示在大量表現miR-146a的細胞株其細胞內之細菌生長數目明顯比對照組少。同時，也利用antagomir抑制內源性miR-146a的表現，結果也發現細胞內之細菌數與對照組間無明顯差異。另一方面，利用西方墨點分析也看到miR-146a會促進autophagy之產生。 以上實驗結果得知，宿主miR-146a的表現，會抑制沙門氏菌在宿主細胞內的生長與複製，此抑制作用是透過autophagy的方式來清除細胞內的細菌。 | zh_TW |
| dc.description.abstract | MicroRNA (miRNA) is a large family of short, non-coding RNAs, which have been discovered playing essential roles in many cellular processes. In mammalian, bacteria have been found to regulate miRNAs during infection progression. Salmonella could invade the non-phagocytic cells and then survive. Salmonella may cause systemic diseases via blood dissemination in infected patients. The intestinal epithelial is the first line of host anti-bacterial defense. Here, we found Salmonella typhimurium infection upregulates the miR-146a expression in human colon cancer epithelial cells, HT29, at 4 hours post infection by TLDA array assay. We further investigate the role of miR-146a in Salmonella infection. We used the colony formation assay to measure the intracellular bacterial numbers post infection in HT29 cells and human intestinal epithelial cells, HIEC. Our results found the enforced expression of miR-146a was restricting Salmonella intracellular replication after Salmonella infection. In contrast, neutralizing miR-146a by specific antagomiR restored Salmonella intracellular replication ability in Salmonella-infected cells. Furthermore, we found the enforced expression of miR-146a increased autophagy. The intracellular bacterial growth results suggest that miR-146a might have a role in Salmonella intracellular survival through xenophagy, was able to clean cytosolic pathogens. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:34:41Z (GMT). No. of bitstreams: 1 ntu-107-D99424004-1.pdf: 5830784 bytes, checksum: af95cce8cfa9ff1fded08eeef39c91f6 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | Contents
Acknowledgement……………………………………………………………………… i 中文摘要………………………………………………………………………………ii Abstract………………………………………………………………………………iii Contents…………………………………………………………………………………v 1 Introduction ……………………………………………………………………1 1.1 microRNA……………………………………………………………………1 1.2 Host microRNAs respond to pathogen infection…………………………2 1.3 Pathogenesis of Salmonella…………………………………………………4 1.4 Host microRNA response to Salmonella infection…………………………15 1.5 Autophagy…………………………………………………………………16 1.6 Objectives…………………………………………………………………25 2 Materials and Methods…………………………………………………………26 2.1 Cell culture and transfection………………………………………………26 2.2 Bacterial Strains and growth conditions……………………………………26 2.3 Bacterial infection…………………………………………………………..27 2.4 Enumeration of intracellular bacteria………………………………………27 2.5 Cell viability assay………………………………………………………….28 2.6 RNA isolation………………………………………………………………28 2.7 Microarray analysis of miRNA expression…………………………………28 2.8 Quantification of miRNAs by qRT-PCR……………………………………29 2.9 Real-time RT-PCR…………………………………………………………30 2.10 Construction of miRNA expression plasmids………………………………30 2.11 Establishment of stably miRNA-expressing cell line………………………30 2.12 MTT cell viability assay……………………………………………………32 2.13 MiR-146a mimic and antagomiR-146a transfection……………………32 2.14 Western blot………………………………………………………………33 2.15 Flow cytometric analysis…………………………………………………33 2.16 NGS analysis of genes expression…………………………………………33 2.17 Statistical analysis…………………………………………………………34 3 Results……………………………………………………………………………35 3.1 Optimization of the Salmonella infection condition in HT29 cell…………35 3.2 Identification of differentially expressed miRNAs during Salmonella infection……………………………………………………………………36 3.3 Investigating the functions of miR-146a, miR-182*, miR-222*, miR-323-3P and miR-376a in Salmonella infection…………………………………….37 3.4 The induction of miR-146a affects the intracellular replication of Salmonella………………………………………………………………38 3.5 MiR-146a affects Salmonella intracellular replication in human intestinal epithelial cells……………………………………………………………39 3.6 AntagomiR-146a eliminates the increase of intracellular replication ability induced by Salmonella infection……………………………………………41 3.7 MiR-146a contributes to Salmonella infection-induced autophagy…42 4 Discussion……………………………………………………………………….43 5 Figures……………………………………………………………………………48 Figure 1. Salmonella infection HT-29 induces host cell apoptosis………………48 Figure 2. miRNAs expression after Salmonella infection………………………50 Figure 3. Establishing the miRNA expressing cell lines………………………53 Figure 4. The miR-146a inhibits Salmonella intracellular replication in HT29 cells……………………………………………………………………54 Figure 5. MiR-146a inhibits Salmonella intracellular replication in HIEC-6 cells…………………………………………………………………56 Figure 6. AntagomiR-146a increases Salmonella intracellular replication in HIEC-6 cells…………………58 Figure 7. MiR-146a promotes autophagy in HT-29 and HIEC-6 cells.….……………………………………………………………59 Figure 8. A model of miR-146a regulatory pathway in Salmonella infection…………………………………………………………61 6 Table. ……………………………………………………………………………63 Table 1. Construction primers list………………………………………………63 7 References………………………………………………………………………65 | - |
| dc.language.iso | en | - |
| dc.title | 宿主微核醣核酸miR-146a抑制沙門氏菌在宿主細胞內的生長與複製 | zh_TW |
| dc.title | The host miR-146a inhibits Salmonella intracellular replication | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 106-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 賴信志;廖淑貞;顏伯勳;蘇剛毅;沈林琥;華國泰 | zh_TW |
| dc.contributor.oralexamcommittee | Hsin-Chih Lai;Shwu-Jen Liaw;;Kang-Yi Su;Sher Singh; | en |
| dc.subject.keyword | 沙門氏菌,微核醣核酸,腸道上皮細胞,胞內繁殖,宿主-病原體交互作用,異源吞噬, | zh_TW |
| dc.subject.keyword | Salmonella,microRNA,intestinal epithelial cells,intracellular replication,host-pathogen interaction,xenophagy, | en |
| dc.relation.page | 80 | - |
| dc.identifier.doi | 10.6342/NTU201802818 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2018-08-15 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | - |
| dc.date.embargo-lift | 2023-10-11 | - |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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