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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃銓珍 | zh_TW |
| dc.contributor.advisor | Chang-Jen Huang | en |
| dc.contributor.author | 顏彰廷 | zh_TW |
| dc.contributor.author | Chang-Ting Yen | en |
| dc.date.accessioned | 2024-03-07T16:23:26Z | - |
| dc.date.available | 2024-03-08 | - |
| dc.date.copyright | 2024-03-07 | - |
| dc.date.issued | 2016 | - |
| dc.date.submitted | 2002-01-01 | - |
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Location of the Prox1 gene expression during newt lens and retina regeneration. Dokl Biol Sci 391, 361-364. Men, R., Wen, M., Dan, X., Zhu, Y., Wang, W., Li, J., Wu, W., Liu, X., and Yang, L. (2015). Nogo-B: A potential indicator for hepatic cirrhosis and regulator in hepatic stellate cell activation. Hepatol Res 45, 113-122. Miao, R.Q., Gao, Y., Harrison, K.D., Prendergast, J., Acevedo, L.M., Yu, J., Hu, F., Strittmatter, S.M., and Sessa, W.C. (2006). Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells. Proc Natl Acad Sci U S A 103, 10997-11002. Nanashima, A., Hatachi, G., Tominaga, T., Murakami, G., Takagi, K., Arai, J., Wada, H., Nagayasu, T., and Sumida, Y. (2016). Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma. Tohoku J Exp Med 238, 9-16. Ober, E.A., Verkade, H., Field, H.A., and Stainier, D.Y. (2006). Mesodermal Wnt2b signalling positively regulates liver specification. Nature 442, 688-691. Oertle, T., Huber, C., van der Putten, H., and Schwab, M.E. (2003a). Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4. J Mol Biol 325, 299-323. Oertle, T., Klinger, M., Stuermer, C.A., and Schwab, M.E. (2003b). A reticular rhapsody: phylogenic evolution and nomenclature of the RTN/Nogo gene family. FASEB J 17, 1238-1247. Qi, B., Qi, Y., Watari, A., Yoshioka, N., Inoue, H., Minemoto, Y., Yamashita, K., Sasagawa, T., and Yutsudo, M. (2003). Pro-apoptotic ASY/Nogo-B protein associates with ASYIP. J Cell Physiol 196, 312-318. Schwab, M.E. (2004). Nogo and axon regeneration. Curr Opin Neurobiol 14, 118-124. Shin, D., Shin, C.H., Tucker, J., Ober, E.A., Rentzsch, F., Poss, K.D., Hammerschmidt, M., Mullins, M.C., and Stainier, D.Y. (2007). Bmp and Fgf signaling are essential for liver specification in zebrafish. Development 134, 2041-2050. Tao, T., and Peng, J. (2009). Liver development in zebrafish (Danio rerio). J Genet Genomics 36, 325-334. Tashiro, K., Satoh, A., Utsumi, T., Chung, C., and Iwakiri, Y. (2013). Absence of Nogo-B (reticulon 4B) facilitates hepatic stellate cell apoptosis and diminishes hepatic fibrosis in mice. Am J Pathol 182, 786-795. Tremblay, K.D., and Zaret, K.S. (2005). Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol 280, 87-99. Wallace, K.N., Yusuff, S., Sonntag, J.M., Chin, A.J., and Pack, M. (2001). Zebrafish hhex regulates liver development and digestive organ chirality. Genesis 30, 141-143. Wanner, M., Lang, D.M., Bandtlow, C.E., Schwab, M.E., Bastmeyer, M., and Stuermer, C.A. (1995). Reevaluation of the growth-permissive substrate properties of goldfish optic nerve myelin and myelin proteins. J Neurosci 15, 7500-7508. Wen, M., Men, R., Yang, Z., Dan, X., Wu, W., Liu, X., and Yang, L. (2015). The Value of Circulating Nogo-B for Evaluating Hepatic Functional Reserve in Patients with Cirrhosis. Dis Markers 2015, 419124. Yiu, G., and He, Z. (2003). Signaling mechanisms of the myelin inhibitors of axon regeneration. Curr Opin Neurobiol 13, 545-551. Zhao, B., Chun, C., Liu, Z., Horswill, M.A., Pramanik, K., Wilkinson, G.A., Ramchandran, R., and Miao, R.Q. (2010). Nogo-B receptor is essential for angiogenesis in zebrafish via Akt pathway. Blood 116, 5423-5433. Zheng, H., Xue, S., Lian, F., and Wang, Y.Y. (2011). A novel promising therapy for vein graft restenosis: overexpressed Nogo-B induces vascular smooth muscle cell apoptosis by activation of the JNK/p38 MAPK signaling pathway. Med Hypotheses 77, 278-281. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/92166 | - |
| dc.description.abstract | Nogo-b也就是大家所熟知的「漿膜蛋白-4b」，在血管受傷後的保護機制中扮演著相當重要的角色。在哺乳類中，Nogo-b會特別表現在肝臟的膽管和非實質細胞裡。肝臟的纖維化和肝內膽管癌(ICC屬於較罕見原發性的肝腫瘤，具有極高度的轉移能力)都會造成Nogo-b表現量的下降。血液中Nogo-b的含量，可以作為肝硬化的有效指標。同時，Nogo-b也能抑制肝臟星狀細胞(HSC)的活性。對於肝細胞，Nogo-b會促進肝細胞的增殖以及肝臟的再生。這些資料讓我們想知道Nogo-b/Nogo受體訊號途徑是否參與斑馬魚肝臟的生長。目前，Nogo-b在肝臟發育中其功能也還未被釐清。
在本篇研究當中，我們收集已培養24、48和72小時的斑馬魚胚胎，透過反義寡核苷酸(MO)抑制和原位雜交技術來分析Nogo-b/Nogo受體對於肝細胞形成和分化的重要性。藉由pHH3免疫染色的結果可以看到抑制Nogo-b的表現能夠阻礙肝細胞增殖。此外，收集注射過Nogo-b-MO的斑馬魚胚胎進行原位雜交分析與對照組比較，結果可以看到Foxa3、Prox1a和Lfabp的表現量有所下降。另一方面，Nogo-b在斑馬魚體內的訊號傳遞，和哺乳類相似，包括三個配位體和四個受體，透過實驗我們確定降低Nogo-b以及其受體的NgR和兩個輔助受體p75和TROY的表現也能夠使斑馬魚的肝臟縮小。因此，我們推測Nogo-B 、NgR、p75和TROY可能形成複合體去影響斑馬魚肝臟的發育。 | zh_TW |
| dc.description.abstract | Nogo-B, also known as Reticulon 4B, plays important roles in vascular injuries. In mammals, Nogo-B is expressed specifically in cholangiocytes and non-parenchymal cells in the liver. Nogo-B expression is down-regulated with the progression of liver fibrosis and in intrahepatic cholangiocarcinoma (ICC), a relatively rare type of primary liver cancer with highly malignant behavior. Circulating Nogo-B may be an effective indicator for liver cirrhosis. Nogo-B inhibition could diminish hepatic stellate cell (HSC) activation. Nogo-B expression in hepatocytes facilitates hepatocyte proliferation and liver regeneration. These data prompt us to consider whether Nogo-B/Nogo receptor signaling participates in the development of the zebrafish liver. So far, its function in the liver development is not understood.
In this study, we characterized the roles of Nogo-B/Nogo receptor in hepatic formation and differentiation by morpholino oligonucleotide (MO) knockdown and whole-mount in situ hybridization with several markers in zebrafish embryos from 24 to 72 hpf. Knockdown of Nogo-B inhibited the proliferation of liver by pHH3 immunostaining. In addition, Nogo-b morphants showed lower expression of foxa3, prox1a and lfabp compared to control MO injected embryos by in situ hybridization. On the other hand, Nogo signaling in zebrafish, like that in mammals, involves three ligands and four receptors. We identified that knockdown of Nogo-B and its receptor-NgR and two coreceptors, p75 and TROY, all decreased liver size during early development. Thus, we hypothesized that Nogo-B/NgR, p75, and TROY will form a complex to be involved in zebrafish liver formation. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-03-07T16:23:26Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-03-07T16:23:26Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | Content I
中文摘要 II Abstract III Abbreviations V Introduction 1 Nogo and Nogo receptor family 1 Nogo-C2 and Nogo receptor complex 3 Liver development in zebrafish 4 Nogo-B expression and liver diseases 5 Specific aims 6 Materials and methods 7 Zebrafish care 7 DNA ligation 7 Transformation 7 Whole-mount in situ hybridization 8 Injection of morpholinos 10 Whole-mount immunostaining 10 Confocal images 12 Q-PCR anlysis 12 Results 13 Nogo-B is required for zebrafish liver development. 13 Reduced expression of genes encoding essential hepatic growth factors in Nogo-B morphants 14 Knockdown of three Nogo coreceptors by morpholino injection resulted in significant block the outgrowth of liver 15 Discussion 17 Figures 19 Table 25 References 27 | - |
| dc.language.iso | en | - |
| dc.subject | Nogo-B | zh_TW |
| dc.subject | zebrafish | zh_TW |
| dc.subject | Nogo-B/Nogo receptor signaling | zh_TW |
| dc.subject | liver development | zh_TW |
| dc.subject | Nogo-B | en |
| dc.subject | 肝臟發育 | en |
| dc.subject | Nogo-B/Nogo受體訊號傳遞 | en |
| dc.subject | 斑馬魚 | en |
| dc.title | 探討斑馬魚Nogo-B訊號傳遞對於斑馬魚肝臟發育所扮演的角色 | zh_TW |
| dc.title | The role of Nogo-B signaling in zebrafish liver development | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 104-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 張茂山;黃聲蘋 | zh_TW |
| dc.contributor.oralexamcommittee | Mau-Sun Chang;Sheng-Ping Huang | en |
| dc.subject.keyword | Nogo-B,zebrafish,Nogo-B/Nogo receptor signaling,liver development, | zh_TW |
| dc.subject.keyword | Nogo-B,斑馬魚,Nogo-B/Nogo受體訊號傳遞,肝臟發育, | en |
| dc.relation.page | 30 | - |
| dc.identifier.doi | 10.6342/NTU201601369 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2016-08-03 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科學研究所 | - |
| 顯示於系所單位： | 生化科學研究所 | |
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