請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66774完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐莞曾 | |
| dc.contributor.author | Chia-Chen Wu | en |
| dc.contributor.author | 吳佳蓁 | zh_TW |
| dc.date.accessioned | 2021-06-17T01:08:17Z | - |
| dc.date.available | 2024-03-12 | |
| dc.date.copyright | 2020-03-12 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-02-01 | |
| dc.identifier.citation | 1. Apovian C.M., Bigornia S., Mott M., et al., Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler Thromb Vasc Biol, 2008. 28: p. 1654.
2. Shulman G.I., Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med, 2014. 371: p. 1131. 3. Patel P. and Abate N., Body fat distribution and insulin resistance. Nutrients, 2013. 5: p. 2019. 4. Friedenstein A.J., Chailakhjan R.K., and Lalykina K.S., The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet, 1970. 3: p. 393. 5. Blau H.M., Brazelton T.R., and Weimann J.M., The evolving concept of a stem cell: entity or function? Cell, 2001. 105: p. 829. 6. Pittenger M.F., Mackay A.M., Beck S.C., et al., Multilineage potential of adult human mesenchymal stem cells. Science, 1999. 284: p. 143. 7. Caplan A.I., Mesenchymal stem cells. J Orthop Res, 1991. 9: p. 641. 8. Horwitz E.M., Le Blanc K., Dominici M., et al., Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy, 2005. 7: p. 393. 9. Rodbell M., Localization of lipoprotein lipase in fat cells of rat adipose tissue J Biol Chem, 1964. 239: p. 753. 10. Zuk P.A., Zhu M., Ashjian P., et al., Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell, 2002. 13: p. 4279. 11. Bourin P., Bunnell B.A., Casteilla L., et al., Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy, 2013. 15: p. 641. 12. Badimon L. and Cubedo J., Adipose tissue depots and inflammation: effects on plasticity and resident mesenchymal stem cell function. Cardiovasc Res, 2017. 113: p. 1064. 13. Zuk P.A., Zhu M., Mizuno H., et al., Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng, 2001. 7: p. 211. 14. Kapur S.K. and Katz A.J., Review of the adipose derived stem cell secretome. Biochimie, 2013. 95: p. 2222. 15. Uzbas F., May I.D., Parisi A.M., et al., Molecular physiognomies and applications of adipose-derived stem cells. Stem Cell Rev Rep, 2015. 11: p. 298. 16. Bartholomew A., Sturgeon C., Siatskas M., et al., Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol, 2002. 30: p. 42. 17. Uccelli A., Moretta L., and Pistoia V., Mesenchymal stem cells in health and disease. Nat Rev Immunol, 2008. 8: p. 726. 18. Yanez R., Lamana M.L., Garcia-Castro J., et al., Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells, 2006. 24: p. 2582. 19. Kebriaei P., Isola L., Bahceci E., et al., Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant, 2009. 15: p. 804. 20. Sun L., Akiyama K., Zhang H., et al., Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells, 2009. 27: p. 1421. 21. Forbes G.M., Sturm M.J., Leong R.W., et al., A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn's disease refractory to biologic therapy. Clin Gastroenterol Hepatol, 2014. 12: p. 64. 22. Papadopoulou A., Yiangou M., Athanasiou E., et al., Mesenchymal stem cells are conditionally therapeutic in preclinical models of rheumatoid arthritis. Ann Rheum Dis, 2012. 71: p. 1733. 23. Djouad F., Plence P., Bony C., et al., Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 2003. 102: p. 3837. 24. Sheng H., Wang Y., Jin Y., et al., A critical role of IFNgamma in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1. Cell Res, 2008. 18: p. 846. 25. Mougiakakos D., Jitschin R., Johansson C.C., et al., The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells. Blood, 2011. 117: p. 4826. 26. Krampera M., Mesenchymal stromal cell 'licensing': a multistep process. Leukemia, 2011. 25: p. 1408. 27. Benvenuto F., Ferrari S., Gerdoni E., et al., Human mesenchymal stem cells promote survival of T cells in a quiescent state. Stem Cells, 2007. 25: p. 1753. 28. Wang Y., Chen X., Cao W., et al., Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol, 2014. 15: p. 1009. 29. Kean T.J., Lin P., Caplan A.I., et al., MSCs: delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int, 2013. 2013: p. 732742. 30. Najar M., Rouas R., Raicevic G., et al., Mesenchymal stromal cells promote or suppress the proliferation of T lymphocytes from cord blood and peripheral blood: the importance of low cell ratio and role of interleukin-6. Cytotherapy, 2009. 11: p. 570. 31. Daneshmandi S., Karimi M.H., and Pourfathollah A.A., TGF-beta1 transduced mesenchymal stem cells have profound modulatory effects on DCs and T cells. Iran J Immunol, 2017. 14: p. 13. 32. Feigenson M., Eliseev R.A., Jonason J.H., et al., PGE2 receptor subtype 1 (EP1) regulates mesenchymal stromal cell osteogenic differentiation by modulating cellular energy metabolism. J Cell Biochem, 2017. 118: p. 4383. 33. Gebler A., Zabel O., and Seliger B., The immunomodulatory capacity of mesenchymal stem cells. Trends Mol Med, 2012. 18: p. 128. 34. Aboalola D. and Han V.K.M., Different effects of insulin-like growth factor-1 and insulin-like growth factor-2 on myogenic differentiation of human mesenchymal stem cells. Stem Cells Int, 2017. 2017: p. 8286248. 35. Su J., Chen X., Huang Y., et al., Phylogenetic distinction of iNOS and IDO function in mesenchymal stem cell-mediated immunosuppression in mammalian species. Cell Death Differ, 2014. 21: p. 388. 36. Stamler J.S., Singel D.J., and Loscalzo J., Biochemistry of nitric oxide and its redox-activated forms. Science, 1992. 258: p. 1898. 37. Sato K., Ozaki K., Oh I., et al., Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood, 2007. 109: p. 228. 38. Ren G., Zhang L., Zhao X., et al., Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell, 2008. 2: p. 141. 39. Ren G., Zhao X., Zhang L., et al., Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol, 2010. 184: p. 2321. 40. Harris R.C., Chung E., and Coffey R.J., EGF receptor ligands. Exp Cell Res, 2003. 284: p. 2. 41. Levano K.S. and Kenny P.A., Clarification of the C-terminal proteolytic processing site of human Amphiregulin. FEBS Letters, 2012. 586: p. 3500. 42. Tanida S., Joh T., Itoh K., et al., The mechanism of cleavage of EGFR ligands induced by inflammatory cytokines in gastric cancer cells. Gastroenterology, 2004. 127: p. 559. 43. Berasain C., Nicou A., Garcia-Irigoyen O., et al., Epidermal growth factor receptor signaling in hepatocellular carcinoma: inflammatory activation and a new intracellular regulatory mechanism. Dig Dis, 2012. 30: p. 524. 44. Berasain C. and Avila M.A., Amphiregulin. Semin Cell Dev Biol, 2014. 28: p. 31. 45. Busser B., Sancey L., Brambilla E., et al., The multiple roles of amphiregulin in human cancer. Biochim Biophys Acta, 2011. 1816: p. 119. 46. Berasain C., Perugorria M.J., Latasa M.U., et al., The epidermal growth factor receptor: a link between inflammation and liver cancer. Exp Biol Med, 2009. 234: p. 713. 47. Qi Y., Operario D.J., Georas S.N., et al., The acute environment, rather than T cell subset pre-commitment, regulates expression of the human T cell cytokine amphiregulin. PLoS One, 2012. 7: p. e39072. 48. Monticelli L.A., Osborne L.C., Noti M., et al., IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc Natl Acad Sci U S A, 2015. 112: p. 10762. 49. Brandl K., Sun L., Neppl C., et al., MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. Proc Natl Acad Sci U S A, 2010. 107: p. 19967. 50. Hsu D., Fukata M., Hernandez Y.G., et al., Toll-like receptor 4 differentially regulates epidermal growth factor-related growth factors in response to intestinal mucosal injury. Lab Invest, 2010. 90: p. 1295. 51. Yang B., Kumoto T., Arima T., et al., Transgenic mice specifically expressing amphiregulin in white adipose tissue showed less adipose tissue mass. Genes Cells, 2018. 23: p. 136. 52. Choi C.H.J. and Cohen P., Adipose crosstalk with other cell types in health and disease. Exp Cell Res, 2017. 360: p. 6. 53. Hotamisligil G.S., Foundations of immunometabolism and implications for metabolic health and disease. Immunity, 2017. 47: p. 406. 54. Lee Y.S., Wollam J., and Olefsky J.M., An integrated view of immunometabolism. Cell, 2018. 172: p. 22. 55. Sell H., Habich C., and Eckel J., Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol, 2012. 8: p. 709. 56. Bluher M., Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes, 2009. 117: p. 241. 57. Cox A.J., West N.P., and Cripps A.W., Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol, 2015. 3: p. 207. 58. Zou J., Lai B., Zheng M., et al., CD4+ T cells memorize obesity and promote weight regain. Cell Mol Immunol, 2018. 15: p. 630. 59. Wu H., Ghosh S., Perrard X.D., et al., T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation, 2007. 115: p. 1029. 60. Kintscher U., Hartge M., Hess K., et al., T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol, 2008. 28: p. 1304. 61. Rausch M.E., Weisberg S., Vardhana P., et al., Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond), 2008. 32: p. 451. 62. Nishimura S., Manabe I., Nagasaki M., et al., CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med, 2009. 15: p. 914. 63. Deiuliis J., Shah Z., Shah N., et al., Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers. PLoS One, 2011. 6: p. e16376. 64. Gimble J.M., Katz A.J., and Bunnell B.A., Adipose-derived stem cells for regenerative medicine. Circ Res, 2007. 100: p. 1249. 65. Cawthorn W.P., Scheller E.L., and MacDougald O.A., Adipose tissue stem cells: the great WAT hope. Trends Endocrinol Metab, 2012. 23: p. 270. 66. Strong A.L., Burow M.E., Gimble J.M., et al., Concise review: The obesity cancer paradigm: exploration of the interactions and crosstalk with adipose stem cells. Stem Cells, 2015. 33: p. 318. 67. Serena C., Keiran N., Ceperuelo-Mallafre V., et al., Obesity and type 2 diabetes alters the immune properties of human adipose derived stem cells. Stem Cells, 2016. 34: p. 2559. 68. Onate B., Vilahur G., Camino-Lopez S., et al., Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype. BMC Genomics, 2013. 14: p. 625. 69. Silva K.R., Liechocki S., Carneiro J.R., et al., Stromal-vascular fraction content and adipose stem cell behavior are altered in morbid obese and post bariatric surgery ex-obese women. Stem Cell Res Ther, 2015. 6: p. 72. 70. Topping D.L. and Clifton P.M., Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev, 2001. 81: p. 1031. 71. Lin H.V., Frassetto A., Kowalik E.J., Jr., et al., Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One, 2012. 7: p. e35240. 72. De Vadder F., Kovatcheva-Datchary P., Goncalves D., et al., Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell, 2014. 156: p. 84. 73. Bloemen J.G., Venema K., van de Poll M.C., et al., Short chain fatty acids exchange across the gut and liver in humans measured at surgery. Clin Nutr, 2009. 28: p. 657. 74. Macfarlane G.T. and Macfarlane S., Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int, 2012. 95: p. 50. 75. Takahashi T., Satou M., Watanabe N., et al., Inhibitory effect of microfibril wheat bran on azoxymethane-induced colon carcinogenesis in CF1 mice. Cancer Lett, 1999. 141: p. 139. 76. Hamer H.M., Jonkers D., Venema K., et al., Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther, 2008. 27: p. 104. 77. Gao Z., Yin J., Zhang J., et al., Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes, 2009. 58: p. 1509. 78. Zhang L., Du J., Yano N., et al., Sodium butyrate protects -against high fat diet-induced cardiac dysfunction and metabolic disorders in type II diabetic mice. J Cell Biochem, 2017. 118: p. 2395. 79. Jin C.J., Sellmann C., Engstler A.J., et al., Supplementation of sodium butyrate protects mice from the development of non-alcoholic steatohepatitis (NASH). Br J Nutr, 2015. 114: p. 1745. 80. Wang X., He G., Peng Y., et al., Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway. Sci Rep, 2015. 5: p. 12676. 81. Le Blanc K., Tammik L., Sundberg B., et al., Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol, 2003. 57: p. 11. 82. Brown A.J., Goldsworthy S.M., Barnes A.A., et al., The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem, 2003. 278: p. 11312. 83. Al-Lahham S.H., Roelofsen H., Priebe M., et al., Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Invest, 2010. 40: p. 401. 84. Taggart A.K., Kero J., Gan X., et al., (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem, 2005. 280: p. 26649. 85. Liu F., Fu Y., Wei C., et al., The expression of GPR109A, NF-kB and IL-1beta in peripheral blood leukocytes from patients with type 2 diabetes. Ann Clin Lab Sci, 2014. 44: p. 443. 86. Davie J.R., Inhibition of histone deacetylase activity by butyrate. J Nutr, 2003. 133: p. 2485s. 87. Vinolo M.A., Rodrigues H.G., Hatanaka E., et al., Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem, 2011. 22: p. 849. 88. Cleophas M.C., Crisan T.O., Lemmers H., et al., Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases. Ann Rheum Dis, 2016. 75: p. 593. 89. Donohoe D.R., Collins L.B., Wali A., et al., The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell, 2012. 48: p. 612. 90. Berni Canani R., Di Costanzo M., and Leone L., The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin Epigenetics, 2012. 4: p. 4. 91. Singh N., Thangaraju M., Prasad P.D., et al., Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J Biol Chem, 2010. 285: p. 27601. 92. Park J., Kim M., Kang S.G., et al., Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol, 2015. 8: p. 80. 93. Chang P.V., Hao L., Offermanns S., et al., The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A, 2014. 111: p. 2247. 94. Sun J., Wu Q., Sun H., et al., Inhibition of histone deacetylase by butyrate protects rat liver from ischemic reperfusion injury. Int J Mol Sci, 2014. 15: p. 21069. 95. Suzuki W., Iizuka S., Tabuchi M., et al., A new mouse model of spontaneous diabetes derived from ddY strain. Exp Anim, 1999. 48: p. 181. 96. Hirayama I., Yi Z., Izumi S., et al., Genetic analysis of obese diabetes in the TSOD mouse. Diabetes, 1999. 48: p. 1183. 97. Pathania R., Ramachandran S., Mariappan G., et al., Combined inhibition of DNMT and HDAC blocks the tumorigenicity of cancer stem-like cells and attenuates mammary tumor growth. Cancer Res, 2016. 76: p. 3224. 98. Frauwirth K.A. and Thompson C.B., Activation and inhibition of lymphocytes by costimulation. J Clin Invest, 2002. 109: p. 295. 99. Chen Z., Huang A., Sun J., et al., Inference of immune cell composition on the expression profiles of mouse tissue. Sci Rep, 2017. 7: p. 40508. 100. Bach M., Schimmelpfennig C., and Stolzing A., Influence of murine mesenchymal stem cells on proliferation, phenotype, vitality, and cytotoxicity of murine cytokine-induced killer cells in coculture. PLoS One, 2014. 9: p. e88115. 101. Zimmerman M.A., Singh N., Martin P.M., et al., Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells. Am J Physiol Gastrointest Liver Physiol, 2012. 302: p. G1405. 102. Mizuno M., Noto D., Kaga N., et al., The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models. PLoS One, 2017. 12: p. e0173032. 103. Smith P.M., Howitt M.R., Panikov N., et al., The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 2013. 341: p. 569. 104. Shigeo Miyata, Nao Yamada, and Kawadab T., Possible involvement of hypothalamic nucleobindin-2 in hyperphagic feeding in Tsumura Suzuki Obese Diabetes mice. Biol. Pharm. Bull., 2012. 35: p. 1784. 105. Onate B., Vilahur G., Ferrer-Lorente R., et al., The subcutaneous adipose tissue reservoir of functionally active stem cells is reduced in obese patients. Faseb j, 2012. 26: p. 4327. 106. Morikawa S., Mabuchi Y., Kubota Y., et al., Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med, 2009. 206: p. 2483. 107. Baer P.C. and Geiger H., Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int, 2012. 2012: p. 812693. 108. Frazier T.P., McLachlan J.B., Gimble J.M., et al., Human adipose-derived stromal/stem cells induce functional CD4+CD25+FoxP3+CD127- regulatory T cells under low oxygen culture conditions. Stem Cells Dev, 2014. 23: p. 968. 109. Yousefi F., Ebtekar M., Soudi S., et al., In vivo immunomodulatory effects of adipose-derived mesenchymal stem cells conditioned medium in experimental autoimmune encephalomyelitis. Immunol Lett, 2016. 172: p. 94. 110. Krampera M., Glennie S., Dyson J., et al., Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood, 2003. 101: p. 3722. 111. Cuerquis J., Romieu-Mourez R., Francois M., et al., Human mesenchymal stromal cells transiently increase cytokine production by activated T cells before suppressing T-cell proliferation: effect of interferon-gamma and tumor necrosis factor-alpha stimulation. Cytotherapy, 2014. 16: p. 191. 112. Bloom D.D., Centanni J.M., Bhatia N., et al., A reproducible immunopotency assay to measure mesenchymal stromal cell-mediated T-cell suppression. Cytotherapy, 2015. 17: p. 140. 113. Eto H., Ishimine H., Kinoshita K., et al., Characterization of human adipose tissue-resident hematopoietic cell populations reveals a novel macrophage subpopulation with CD34 expression and mesenchymal multipotency. Stem Cells Dev, 2013. 22: p. 985. 114. Eljaafari A., Robert M., Chehimi M., et al., Adipose tissue-derived stem cells from obese subjects contribute to inflammation and reduced insulin response in adipocytes through differential regulation of the Th1/Th17 balance and monocyte activation. Diabetes, 2015. 64: p. 2477. 115. Liu M.H., Li Y., Han L., et al., Adipose-derived stem cells were impaired in restricting CD4(+)T cell proliferation and polarization in type 2 diabetic ApoE(-/-) mouse. Mol Immunol, 2017. 87: p. 152. 116. Pinchuk L.M. and Filipov N.M., Differential effects of age on circulating and splenic leukocyte populations in C57BL/6 and BALB/c male mice. Immun Ageing, 2008. 5: p. 1. 117. Kadle R.L., Abdou S.A., Villarreal-Ponce A.P., et al., Microenvironmental cues enhance mesenchymal stem cell-mediated immunomodulation and regulatory T-cell expansion. PLoS One, 2018. 13: p. e0193178. 118. Zhilai Z., Biling M., Sujun Q., et al., Preconditioning in lowered oxygen enhances the therapeutic potential of human umbilical mesenchymal stem cells in a rat model of spinal cord injury. Brain Res, 2016. 1642: p. 426. 119. Lan Y.W., Choo K.B., Chen C.M., et al., Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced pulmonary fibrosis. Stem Cell Res Ther, 2015. 6: p. 97. 120. Krampera M., Cosmi L., Angeli R., et al., Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells, 2006. 24: p. 386. 121. Hemeda H., Jakob M., Ludwig A.K., et al., Interferon-gamma and tumor necrosis factor-alpha differentially affect cytokine expression and migration properties of mesenchymal stem cells. Stem Cells Dev, 2010. 19: p. 693. 122. Lim J., Lee S., Ju H., et al., Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells. Int J Mol Med, 2017. 40: p. 739. 123. Wang B., Lin Y., Hu Y., et al., mTOR inhibition improves the immunomodulatory properties of human bone marrow mesenchymal stem cells by inducing COX-2 and PGE2. Stem Cell Res Ther, 2017. 8: p. 292. 124. Li D., Wang P., Li Y., et al., All-trans retinoic acid improves the effects of bone marrow-derived mesenchymal stem cells on the treatment of ankylosing spondylitis: an in vitro study. Stem Cells Int, 2015. 2015: p. 484528. 125. Zaiss D.M., Yang L., Shah P.R., et al., Amphiregulin, a TH2 cytokine enhancing resistance to nematodes. Science, 2006. 314: p. 1746. 126. Carney K., Chang Y.R., Wilson S., et al., Regulatory T-cell-intrinsic amphiregulin is dispensable for suppressive function. J Allergy Clin Immunol, 2016. 137: p. 1907. 127. Kim S.W., Hooker J.M., Otto N., et al., Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET. Nucl Med Biol, 2013. 40: p. 912. 128. Miller A.A., Kurschel E., Osieka R., et al., Clinical pharmacology of sodium butyrate in patients with acute leukemia. Eur J Cancer Clin Oncol, 1987. 23: p. 1283. 129. Ooi C.C., Good N.M., Williams D.B., et al., Structure-activity relationship of butyrate analogues on apoptosis, proliferation and histone deacetylase activity in HCT-116 human colorectal cancer cells. Clin Exp Pharmacol Physiol, 2010. 37: p. 905. 130. Almotairy A.R.Z., Gandin V., Morrison L., et al., Antitumor platinum(IV) derivatives of carboplatin and the histone deacetylase inhibitor 4-phenylbutyric acid. J Inorg Biochem, 2017. 177: p. 1. 131. Kang S.N., Lee E., Lee M.K., et al., Preparation and evaluation of tributyrin emulsion as a potent anti-cancer agent against melanoma. Drug Deliv, 2011. 18: p. 143. 132. Prabhakar U., Maeda H., Jain R.K., et al., Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res, 2013. 73: p. 2412. 133. Minelli R., Occhipinti S., Gigliotti C.L., et al., Solid lipid nanoparticles of cholesteryl butyrate inhibit the proliferation of cancer cells in vitro and in vivo models. Br J Pharmacol, 2013. 170: p. 233. 134. Nilsson A.C., Ostman E.M., Knudsen K.E., et al., A cereal-based evening meal rich in indigestible carbohydrates increases plasma butyrate the next morning. J Nutr, 2010. 140: p. 1932. 135. Huang L., Targeting histone deacetylases for the treatment of cancer and inflammatory diseases. J Cell Physiol, 2006. 209: p. 611. 136. Chen X., Barozzi I., Termanini A., et al., Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages. Proc Natl Acad Sci U S A, 2012. 109: p. E2865. 137. Gao Z., He Q., Peng B., et al., Regulation of nuclear translocation of HDAC3 by IkappaBalpha is required for tumor necrosis factor inhibition of peroxisome proliferator-activated receptor gamma function. J Biol Chem, 2006. 281: p. 4540. 138. Usui T., Okada M., Mizuno W., et al., HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats. Am J Physiol Heart Circ Physiol, 2012. 302: p. H1894. 139. Yan B., Liu Y., Bai H., et al., HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies. Theranostics, 2017. 7: p. 1002. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66774 | - |
| dc.description.abstract | 研究背景
代謝症候群是指一群容易導致心血管疾病的危險因子聚集，包含腹部肥胖、高血糖、高血壓、高三酸甘油脂及高密度脂蛋白膽固醇偏低。其中，肥胖會誘導促發炎因子產生進而改變脂肪組織的結構和組成，包括脂肪細胞、免疫細胞和脂肪幹細胞 (adipose-derived stem cells, ASC)。ASC已被證實具有調控免疫系統的潛力，但取決於生理環境的條件，在發炎環境下ASC將失去調控功能。短鏈脂肪酸為腸道菌發酵代謝後的主要產物，包含乙酸、丙酸、丁酸和戊酸。這些短鏈脂肪酸除了可以提供腸道能量外，也具有調控免疫系統的作用。許多文獻指出丁酸抑制發炎效果最為顯著，並在脂肪組織中表現出多種調節功能。本論文假設丁酸具有調控免疫系統的能力且可以增加ASC免疫抑制的功能，進而恢復因代謝疾病而失去調控功能的ASC。 實驗方法與結果 利用3H-thymidine incorporation assay測定脾臟細胞經抗體CD3/28刺激之增生反應，結果顯示丁酸增強ASC體外抑制T細胞增生的能力。為了證實丁酸在動物模式具有同樣的作用，本論文將BALB/c小鼠隨機分成3組，分別給予正常飲用水、含100 mM丁酸及200 mM丁酸的飲用水。第21天後，犧牲取各組之ASC分別命名為ASCCtl、ASCBA100mM和ASCBA200mM進行測試，計算免疫抑制百分比；結果顯示ASCBA200Mm具有更強的免疫抑制能力 (ASCBA200mM = 54% vs. ASCCtl = 25%, P < 0.001)。機轉探討方面，以即時定量聚合酶連鎖反應、西方點墨法及酵素沉澱法測定一氧化氮合成酶 (inducible nitric oxide synthase, iNOS) 和雙調蛋白 (amphiregulin, Areg) 基因與蛋白質表現量。綜合實驗結果顯示，有T細胞增生的發炎環境下，ASCCtl加丁酸或ASCBA200mM的組別與ASCCtl相比，iNOS和Areg基因與蛋白質表現量都顯著上升。此外，利用組蛋白乙醯化程度來探討丁酸調控ASC之分生機制。結果顯示ASCCtl加丁酸或ASCBA200mM的組別與ASCCtl相比，組蛋白乙醯化表現量顯著上升，並且能影響組蛋白去乙醯酶之基因。 為了進一步探討丁酸在疾病模式小鼠身上的療效，本論文將可代表人類代謝症候群疾病的 Tsumura, Suzuki, Obese Diabetes (TSOD) 小鼠隨機分成2組：植入丁酸錠劑及無錠劑植入，另以同品系之Tsumura, Suzuki, Non Obese小鼠做為控制組。植入錠劑第42天後分離各組的ASC。3H-thymidine incorporation assay測定顯示，代謝疾病會降低ASC免疫抑制能力，植入丁酸錠劑則恢復TSOD小鼠ASC的免疫抑制能力。 結論 本論文實驗結果顯示丁酸體外加入或是於動物體內投予，增強ASC體外的免疫抑制能力並恢復代謝疾病中ASC免疫抑制的效果，可能是藉由丁酸增加ASC之iNOS及Areg表現。此外，丁酸增加ASC之組蛋白乙醯化的表現，並影響蛋白去乙醯酶的基因變化。在未來發展上建議可利用丁酸增強ASC免疫能力的方式來改善肥胖之脂肪發炎環境。 | zh_TW |
| dc.description.abstract | Background
Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors, including visceral obesity, hypertension, insulin resistance, and dyslipidemia. Among them, visceral obesity is the most prevalent form of the MetS. Moreover, obesity ensues a pro-inflammatory environment which changes the structure and composition of the adipose tissue, including adipose-derived stem cells (ASC). ASC have been recognized to exhibit extensive immunomodulatory properties; however, ASC can be beneficial or detrimental to health depending on the environment conditions. Short-chain fatty acids (SCFA) are derived from the microbial fermentation of dietary fibers in the colon. Among the SCFA, butyrate has received remarkable attention for its multiple beneficial effects ranging from the intestinal tract to the peripheral tissues. In addition, butyrate exerts potent anti-inflammatory effects and exhibits multiple regulatory function in the adipose tissue. Thus, we aim to study whether butyrate enhances ASC’s immunosuppressive potency. Method and Result For immunosuppressive assay of ASC, the in vitro proliferation study of anti-CD3/28-activated splenocytes, was evaluated by 3H-thymidine incorporation assay. We have demonstrated that butyrate enhanced the immunosuppressive potency of ASC. Next, we investigated whether butyrate could exert the same effects on ASC when it is administered orally to mice. BALB/c mice were divided into three groups randomly: the first group of mice were provided with regular drinking water; the second and the third groups were provided with 100 mM or 200 mM sodium butyrate in drinking water for 21 days, respectively. At the end of the treatment protocol, mice were sacrificed and ASC were isolated from mice in each group, designated as ASCCtl, ASCBA100mM, and ASCBA200mM. In immunosuppressive assay, the results were reported as percent suppression and showed that oral butyrate supplementation significantly enhanced the ex vivo suppressive potency of ASC (ASCBA200mM = 54% vs. ASCCtl = 25%, P < 0.001). Furthermore, western blot and quantitative PCR analysis revealed both ASCCtl with butyrate and ASCBA200mM had a higher gene level of inducible nitric oxide synthase (iNOS) and amphiregulin (Areg) than ASCCtl in inflammatory milieu. Besides, butyrate treatment induced higher level of acetyl histone than ASCCtl and affected different isoforms of histone deacetylase (HDAC) on ASC. To further evaluated the treatment of butyrate in MetS, we used butyrate pellet to treat Tsumura, Suzuki, Obese Diabetes (TSOD) mice for 42 days. The immunosuppressive assay data showed ASC of TSOD had lower suppressive potency than healthy mice. However, the butyrate treatment repaired immunosuppressive function of ASC. Conclusion Our findings suggested that butyrate treatment beneficially affected ASC in animal models, partly through enhanced immunosuppressive potency accompanied by up-regulated iNOS and Areg expression. Moreover, our data showed that butyrate affected different types of HDAC on ASC. This work provides underlying information that enhancement of ASC’s immunosuppression by butyrate is a useful tool to improve inflammation of adipose tissue in obesity. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T01:08:17Z (GMT). No. of bitstreams: 1 ntu-109-R06423031-1.pdf: 2725259 bytes, checksum: 66a808c15460b7ee930353e887933e32 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 誌謝 ii
目 錄 iii 圖目錄 v 表目錄 vi 中文摘要 vii Abstract ix 第一章 緒論 1 壹、 幹細胞簡介 1 貳、 丁酸簡介 6 參、 研究目的 8 肆、 附圖 9 第二章 實驗材料與方法 11 壹、 實驗材料 11 貳、 實驗方法 16 第三章 結果 24 壹、 脂肪幹細胞之表面抗原分析 24 貳、 丁酸對脂肪幹細胞體外之免疫抑制能力的作用 24 參、 小鼠口服丁酸模式對脂肪幹細胞之免疫抑制能力的影響 25 肆、 丁酸對脂肪幹細胞之iNOS和Areg基因變化的影響 26 伍、 丁酸對脂肪幹細胞之組蛋白去乙醯酶表現量的影響 27 陸、 代謝疾病動物模式中丁酸對脂肪幹細胞之免疫抑制能力的效果 29 第四章 討論 30 壹、 脂肪幹細胞之特性 30 貳、 脂肪幹細胞與免疫抑制能力 30 參、 代謝疾病與脂肪幹細胞免疫抑制能力的影響與治療 31 肆、 丁酸與脂肪幹細胞之免疫抑制作用 33 伍、 丁酸作用於體內的限制及改善 33 陸、 丁酸對脂肪幹細胞之HDAC基因可能的影響 34 第五章 結論與展望 36 第六章 參考文獻 37 第七章 圖表 48 | |
| dc.language.iso | zh-TW | |
| dc.subject | 丁酸 | zh_TW |
| dc.subject | 組蛋白去乙醯? | zh_TW |
| dc.subject | 雙調蛋白 | zh_TW |
| dc.subject | 一氧化氮合成? | zh_TW |
| dc.subject | 免疫調控 | zh_TW |
| dc.subject | 脂肪幹細胞 | zh_TW |
| dc.subject | Areg | en |
| dc.subject | iNOS | en |
| dc.subject | adipose-derived stem cells | en |
| dc.subject | immunomodulation | en |
| dc.subject | HDAC | en |
| dc.subject | butyrate | en |
| dc.title | 丁酸調控脂肪幹細胞之免疫抑制能力與機轉探討 | zh_TW |
| dc.title | Functional and Mechanistic Studies of Butyrate Effects
on Immunosuppression of Adipose-derived Stem Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孔繁璐,黃偉展 | |
| dc.subject.keyword | 脂肪幹細胞,丁酸,免疫調控,一氧化氮合成?,雙調蛋白,組蛋白去乙醯?, | zh_TW |
| dc.subject.keyword | adipose-derived stem cells,butyrate,immunomodulation,iNOS,Areg,HDAC, | en |
| dc.relation.page | 56 | |
| dc.identifier.doi | 10.6342/NTU202000151 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-02-04 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-109-1.pdf 未授權公開取用 | 2.66 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。