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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳寬墩(Kwan-Dun Wu) | |
dc.contributor.author | Shao-Yu Yang | en |
dc.contributor.author | 楊紹佑 | zh_TW |
dc.date.accessioned | 2021-06-16T09:55:24Z | - |
dc.date.available | 2017-03-01 | |
dc.date.copyright | 2017-03-01 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-12-29 | |
dc.identifier.citation | Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X, Tian B, Wagner T, Vatner SF, Sadoshima J. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res. 2007 May 25;100(10):1512-21.
Baur JA, Ungvari Z, Minor RK, Le Couteur DG, de Cabo R. Are sirtuins viable targets for improving healthspan and lifespan? Nat Rev Drug Discov. 2012 Jun 1;11(6):443-61. Breitenstein A, Wyss CA, Spescha RD, Franzeck FC, Hof D, Riwanto M, Hasun M, Akhmedov A, von Eckardstein A, Maier W, Landmesser U, Lüscher TF, Camici GG. Peripheral blood monocyte Sirt1 expression is reduced in patients with coronary artery disease. PLoS One. 2013;8(1):e53106. Brooks CL, Gu W. How does SIRT1 affect metabolism, senescence and cancer? Nat Rev Cancer. 2009 Feb;9(2):123-8. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME. Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase. Science 2004 Mar 26;303(5666):2011-5 Cantó C, Auwerx J. Caloric restriction, SIRT1 and longevity. Trends Endocrinol Metab. 2009 Sep;20(7):325-31. Cantó C, Auwerx J. Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)? Pharmacol Rev. 2012 Jan;64(1):166-87. Chen YM, Chien CT, Hu-Tsai MI, Wu KD, Tsai CC, Wu MS, Tsai TJ. Pentoxifylline attenuates experimental mesangial proliferative glomerulonephritis. Kidney Int. 1999 Sep;56(3):932-43. Chen WY, Wang DH, Yen RC, Luo J, Gu W, Baylin SB. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell. 2005 Nov 4;123(3):437-48. Chevalier RL, Forbes MS, Thornhill BA. Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int. 2009 Jun;75(11):1145-52. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004 Jul 16;305(5682):390-2. de Kreutzenberg SV, Ceolotto G, Papparella I, Bortoluzzi A, Semplicini A, Dalla Man C, Cobelli C, Fadini GP, Avogaro A. Downregulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms. Diabetes. 2010 Apr;59(4):1006-15. Deng XQ, Chen LL, Li NX. The expression of SIRT1 in nonalcoholic fatty liver disease induced by high-fat diet in rats. Liver Int. 2007 Jun;27(5):708-15 Dong YJ, Liu N, Xiao Z, Sun T, Wu SH, Sun WX, Xu ZG, Yuan H. Renal protective effect of sirtuin 1. J Diabetes Res. 2014;2014:843786 Dworkin LD1, Benstein JA, Tolbert E, Feiner HD. Salt restriction inhibits renal growth and stabilizes injury in rats with established renal disease. J Am Soc Nephrol. 1996 Mar;7(3):437-42. Esteban V, Lorenzo O, Rupérez M, Suzuki Y, Mezzano S, Blanco J, Kretzler M, Sugaya T, Egido J, Ruiz-Ortega M. Angiotensin II, via AT1 and AT2 receptors and NF-kappaB pathway, regulates the inflammatory response in unilateral ureteral obstruction. J Am Soc Nephrol. 2004 Jun;15(6):1514-29. Fan H, Yang HC, You L, Wang YY, He WJ, Hao CM. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int. 2013 Mar;83(3):404-13. Fan YY, Kohno M, Hitomi H, Kitada K, Fujisawa Y, Yatabe J, Yatabe M, Felder RA, Ohsaki H, Rafiq K, Sherajee SJ, Noma T, Nishiyama A, Nakano D. Aldosterone/Mineralocorticoid Receptor Stimulation Induces Cellular Senescence in the Kidney. Endocrinology. 2011 Feb;152(2):680-8. Finkel T, Deng CX, Mostoslavsky R. Recent progress in the biology and physiology of sirtuins. Nature. 2009 Jul 30;460(7255):587-91. Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, Bhimavarapu A, Luikenhuis S, de Cabo R, Fuchs C, Hahn WC, Guarente LP, Sinclair DA. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One. 2008 Apr 16;3(4):e2020. Fontana L, Partridge L, Longo VD. Extending healthy life span–from yeast to humans. Science. 2010 Apr 16;328(5976):321-6.. Fujitsuka N, Asakawa A, Morinaga A, Amitani MS, Amitani H, Katsuura G, Sawada Y, Sudo Y, Uezono Y, Mochiki E, Sakata I, Sakai T, Hanazaki K, Yada T, Yakabi K, Sakuma E, Ueki T, Niijima A, Nakagawa K, Okubo N, Takeda H, Asaka M, Inui A. Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1. Mol Psychiatry. 2016 Nov;21(11):1613-1623. Funk JA, Schnellmann RG. Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia-reperfusion injury. Toxicol Appl Pharmacol. 2013 Dec 1;273(2):345-54. Gao R, Chen J, Hu Y, Li Z, Wang S, Shetty S, Fu J. Sirt1 deletion leads to enhanced inflammation and aggravates endotoxin-induced acute kidney injury. PLoS One. 2014 Jun 4;9(6):e98909. González-Cuadrado S, Bustos C, Ruiz-Ortega M, Ortiz A, Guijarro C, Plaza JJ, Egido J. Expression of leucocyte chemoattractants by interstitial renal fibroblasts: up-regulation by drugs associated with interstitial fibrosis. Clin Exp Immunol. 1996 Dec;106(3):518-22. Guarente L, Picard F. Calorie restriction--the SIR2 connection. Cell. 2005 Feb 25;120(4):473-82. Grande MT, López-Novoa JM. Fibroblast activation and myofibroblast generation in obstructive nephropathy. Nat Rev Nephrol. 2009 Jun;5(6):319-28. Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H, Washida N, Tokuyama H, Hayashi K, Itoh H. Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression. Biochem Biophys Res Commun. 2008 Jul 18;372(1):51-6. Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H, Sueyasu K, Washida N, Tokuyama H, Tzukerman M, Skorecki K, Hayashi K, Itoh H. Kidney-specific overexpression of Sirt1 protects against acute kidney injury by retaining peroxisome function. J Biol Chem. 2010 Apr 23;285(17):13045-56. Hasegawa K, Wakino S, Simic P, Sakamaki Y, Minakuchi H, Fujimura K, Hosoya K, Komatsu M, Kaneko Y, Kanda T, Kubota E, Tokuyama H, Hayashi K, Guarente L, Itoh H. Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes. Nat Med. 2013 Nov;19(11):1496-504. He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, Yang HC, Fogo AB, Zent R, Harris RC, Breyer MD, Hao CM. Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest. 2010 Apr;120(4):1056-68. Hwang JW, Yao H, Caito S, Sundar IK, Rahman I. Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med. 2013 Aug;61:95-110. Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795-800. Javkhedkar AA, Banday AA. Antioxidant resveratrol restores renal sodium transport regulation in SHR. Physiol Rep. 2015 Nov;3(11). pii: e12618. Kaeberlein M1, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999 Oct 1;13(19):2570-80. Kanfi Y, Peshti V, Gozlan YM, Rathaus M, Gil R, Cohen HY. Regulation of SIRT1 protein levels by nutrient availability. FEBS Lett. 2008 Jul 9;582(16):2417-23. Katto J, Engel N, Abbas W, Herbein G, Mahlknecht U. Transcription factor NF-κB regulates the expression of the histone deacetylase SIRT1. Clin Epigenetics. 2013 Jul 19;5(1):11. Kemp BA, Howell NL, Gray JT, Keller SR, Nass RM, Padia SH. Intrarenal ghrelin infusion stimulates distal nephron-dependent sodium reabsorption in normal rats. Hypertension. 2011 Mar;57(3):633-9. Kemp BA, Howell NL, Gildea JJ, Keller SR, Padia SH. Intrarenal ghrelin receptors regulate ENaC-dependent sodium reabsorption by a cAMP-dependent pathway. Kidney Int. 2013 Sep;84(3):501-8. Khader A, Yang WL, Kuncewitch M, Jacob A, Prince JM, Asirvatham JR, Nicastro J, Coppa GF, Wang P. Sirtuin 1 activation stimulates mitochondrial biogenesis and attenuates renal injury after ischemia-reperfusion. Transplantation. 2014 Jul 27;98(2):148-56 Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J. 2007 Jul 11;26(13):3169-79. Kim EJ, Kho JH, Kang MR, Um SJ. Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity. Mol Cell. 2007 Oct 26;28(2):277-90. Kim JE, Chen J, Lou Z. DBC1 is a negative regulator of SIRT1. Nature. 2008 Jan 31;451(7178):583-6 Kitada M, Takeda A, Nagai T, Ito H, Kanasaki K, Koya D. Dietary restriction ameliorates diabetic nephropathy through anti-Inflammatory effects and regulation of the autophagy via restoration of Sirt1 in diabetic Wistar fatty (fa/fa) rats: a model of type 2 diabetes. Exp Diabetes Res. 2011;2011:908185. Kitada M, Kume S, Takeda-Watanabe A, Kanasaki K, Koya D. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy. Clin Sci (Lond). 2013 Feb;124(3):153-64. Kitada M, Koya D. SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential. Diabetes Metab J. 2013 Oct;37(5):315-25. Klahr S, Morrissey J. Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol. 2002 Nov;283(5):F861-75. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999 Dec 9;402(6762):656-60. Kong L, Wu H, Zhou W, Luo M, Tan Y, Miao L, Cai L. Sirtuin 1: A Target for Kidney Diseases. Mol Med. 2015 Jan 12;21:87-97. Kumar R, Chaterjee P, Sharma PK, Singh AK, Gupta A, Gill K, Tripathi M, Dey AB, Dey S. Sirtuin1: a promising serum protein marker for early detection of Alzheimer's disease. PLoS One. 2013 Apr 16;8(4):e61560. Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isshiki K, Isono M, Uzu T, Guarente L, Kashiwagi A, Koya D. SIRT1 inhibits transforming growth factor beta-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation. J Biol Chem. 2007 Jan 5;282(1):151-8. Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isono M, Isshiki K, Uzu T, Kashiwagi A, Koya D. Silent information regulator 2 (SIRT1) attenuates oxidative stress-induced mesangial cell apoptosis via p53 deacetylation. Free Radic Biol Med. 2006 Jun 15;40(12):2175-82. Lavu S, Boss O, Elliott PJ, Lambert PD. Sirtuins--novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov. 2008 Oct;7(10):841-53. Li J, Qu X, Ricardo SD, Bertram JF, Nikolic-Paterson DJ. Resveratrol inhibits renal fibrosis in the obstructed kidney: potential role in deacetylation of Smad3. Am J Pathol. 2010 Sep;177(3):1065-71. Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell. 2010 Jun 25;38(6):864-78. Lin SL, Chen YM, Chien CT, Chiang WC, Tsai CC, Tsai TJ. Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. J Am Soc Nephrol. 2002 Dec;13(12):2916-29. Lin SL, Chen RH, Chen YM, Chiang WC, Lai CF, Wu KD, Tsai TJ. Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor. J Am Soc Nephrol. 2005 Sep;16(9):2702-13. Lin SL, Kisseleva T, Brenner DA, Duffield JS. Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol. 2008 Dec;173(6):1617-27. Lin SL, Castaño AP, Nowlin BT, Lupher ML Jr, Duffield JS. Bone marrow Ly6Chigh monocytes are selectively recruited to injured kidney and differentiate into functionally distinct populations. J Immunol. 2009 Nov 15;183(10):6733-43. Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science. 2000 Sep 22;289(5487):2126-8. Liu T, Liu PY, Marshall GM. The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res. 2009 Mar 1;69(5):1702-5. Maeda S, Koya D, Araki S, Babazono T, Umezono T, Toyoda M, Kawai K, Imanishi M, Uzu T, Suzuki D, Maegawa H, Kashiwagi A, Iwamoto Y, Nakamura Y. Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes. Clin Exp Nephrol. 2011 Jun;15(3):381-90 Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, DeRicco J, Kasuno K, Irani K. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14855-60. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29;450(7170):712-6. Miyazaki R, Ichiki T, Hashimoto T, Inanaga K, Imayama I, Sadoshima J, Sunagawa K. SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1263-9. Morris BJ. Seven sirtuins for seven deadly diseases of aging. Free Radic Biol Med. 2013 Mar;56:133-71. Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, Mukoyama M, Sugawara A, Hosoda H, Kojima M, Kangawa K, Nakao K. Kidney produces a novel acylated peptide, ghrelin. FEBS Lett. 2000 Dec 15;486(3):213-6. Ni J, Shen Y, Wang Z, Shao DC, Liu J, Fu LJ, Kong YL, Zhou L, Xue H, Huang Y, Zhang W, Yu C, Lu LM. Inhibition of STAT3 acetylation is associated with attenuated renal fibrosis in the obstructed kidney. Acta Pharmacol Sin. 2014 Aug;35(8):1045-54. Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA, Pfluger PT, Tschöp MH. Sirtuin 1 and sirtuin 3: physiological modulators of metabolism. Physiol Rev. 2012 Jul;92(3):1479-514. Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, Hartlerode A, Stegmuller J, Hafner A, Loerch P, Wright SM, Mills KD, Bonni A, Yankner BA, Scully R, Prolla TA, Alt FW, Sinclair DA. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 2008 Nov 28;135(5):907-18. Orimo M, Minamino T, Miyauchi H, Tateno K, Okada S, Moriya J, Komuro I. Protective role of SIRT1 in diabetic vascular dysfunction. Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):889-94 Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ. Nature. 2004 Jun 17;429(6993):771-6 Ponnusamy M, Zhou X, Yan Y, Tang J, Tolbert E, Zhao TC, Gong R, Zhuang S. Blocking sirtuin 1 and 2 inhibits renal interstitial fibroblast activation and attenuates renal interstitial fibrosis in obstructive nephropathy. J Pharmacol Exp Ther. 2014 Aug;350(2):243-56. Ponnusamy M, Zhuang MA, Zhou X, Tolbert E, Bayliss G, Zhao TC, Zhuang S. Activation of Sirtuin-1 Promotes Renal Fibroblast Activation and Aggravates Renal Fibrogenesis. J Pharmacol Exp Ther. 2015 Aug;354(2):142-51. Rabbani N, Sebekova K, Sebekova K Jr, Heidland A, Thornalley PJ. Accumulation of free adduct glycation, oxidation, and nitration products follows acute loss of renal function. Kidney Int. 2007 Nov;72(9):1113-21 Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008 Apr 15;177(8):861-70. Rogina B, Helfand SL. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15998-6003 Satoh M, Kashihara N, Yamasaki Y, Maruyama K, Okamoto K, Maeshima Y, Sugiyama H, Sugaya T, Murakami K, Makino H. Renal interstitial fibrosis is reduced in angiotensin II type 1a receptor-deficient mice. J Am Soc Nephrol. 2001 Feb;12(2):317-25. Schug TT, Xu Q, Gao H, Peres-da-Silva A, Draper DW, Fessler MB, Purushotham A, Li X. Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress. Mol Cell Biol. 2010 Oct;30(19):4712-21. Simic P, Williams EO, Bell EL, Gong JJ, Bonkowski M, Guarente L. SIRT1 suppresses the epithelial-to-mesenchymal transition in cancer metastasis and organ fibrosis. Cell Rep. 2013 Apr 25;3(4):1175-86. Sinclair DA, Guarente L. Extrachromosomal rDNA circles--a cause of aging in yeast. Cell. 1997 Dec 26;91(7):1033-42. Shore D, Squire M, Nasmyth KA. Characterization of two genes required for the position-effect control of yeast mating-type genes. EMBO J. 1984 Dec 1;3(12):2817-23. Song R, Xu W, Chen Y, Li Z, Zeng Y, Fu Y. The expression of Sirtuins 1 and 4 in peripheral blood leukocytes from patients with type 2 diabetes. Eur J Histochem. 2011 Mar 21;55(1):e10 Strom BL, Anderson CA, Ix JH. Sodium reduction in populations: insights from the Institute of Medicine committee. JAMA. 2013 Jul 3;310(1):31-2. Tikoo K, Tripathi DN, Kabra DG, Sharma V, Gaikwad AB. Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53. FEBS Lett. 2007 Mar 6;581(5):1071-8. Tikoo K, Singh K, Kabra D, Sharma V, Gaikwad A. Change in histone H3 phosphorylation, MAP kinase p38, SIR 2 and p53 expression by resveratrol in preventing streptozotocin induced type I diabetic nephropathy. Free Radic Res. 2008 Apr;42(4):397-404. Tissenbaum HA, Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature. 2001 Mar 8;410(6825):227-30 Tsai YF, Yu HP, Chang WY, Liu FC, Huang ZC, Hwang TL. Sirtinol inhibits neutrophil elastase activity and attenuates lipopolysaccharide-mediated acute lung injury in mice. Sci Rep. 2015 Feb 10;5:8347. Vasko R, Xavier S, Chen J, Lin CH, Ratliff B, Rabadi M, Maizel J, Tanokuchi R, Zhang F, Cao J, Goligorsky MS. Endothelial sirtuin 1 deficiency perpetrates nephrosclerosis through downregulation of matrix metalloproteinase-14: relevance to fibrosis of vascular senescence. J Am Soc Nephrol. 2014 Feb;25(2):276-91. Velásquez DA, Martínez G, Romero A, Vázquez MJ, Boit KD, Dopeso-Reyes IG, López M, Vidal A, Nogueiras R, Diéguez C. The central Sirtuin 1/p53 pathway is essential for the orexigenic action of ghrelin. Diabetes. 2011 Apr;60(4):1177-85. Wakino S, Hasegawa K, Itoh H. Sirtuin and metabolic kidney disease. Kidney Int. 2015 Oct;88(4):691-8. Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, Kim S, Xu X, Zheng Y, Chilton B, Jia R, Zheng ZM, Appella E, Wang XW, Ried T, Deng CX. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008 Oct 7;14(4):312-23. Wang ZL, Luo XF, Li MT, Xu D, Zhou S, Chen HZ, Gao N, Chen Z, Zhang LL, Zeng XF. Resveratrol possesses protective effects in a pristane-induced lupus mouse model. PLoS One. 2014 Dec 11;9(12):e114792. Wen D, Huang X, Zhang M, Zhang L, Chen J, Gu Y, Hao CM. Resveratrol attenuates diabetic nephropathy via modulating angiogenesis. PLoS One. 2013 Dec 3;8(12):e82336. Yang XD, Tajkhorshid E, Chen LF. Functional interplay between acetylation and methylation of the RelA subunit of NF-kappaB. Mol Cell Biol. 2010 May;30(9):2170-80. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW. Modulation of NF-B-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004 Jun 16;23(12):2369-80. Zhang D, Li S, Cruz P, Kone BC. Sirtuin 1 functionally and physically interacts with disruptor of telomeric silencing-1 to regulate alpha-ENaC transcription in collecting duct. J Biol Chem. 2009 Jul 31;284(31):20917-26. Zhang QJ, Wang Z, Chen HZ, Zhou S, Zheng W, Liu G, Wei YS, Cai H, Liu DP, Liang CC. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res. 2008 Nov 1;80(2):191-9. Zhao W, Kruse JP, Tang Y, Jung SY, Qin J, Gu W. Negative regulation of the deacetylase SIRT1 by DBC1. Nature. 2008 Jan 31;451(7178):587-90. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60090 | - |
dc.description.abstract | Sirtuin 1(Sirt1)是一個依賴菸鹼醯胺腺嘌呤二核酸以進行作用的去乙醯基酶,已知與許多細胞活動相關。之前的研究顯示sirtuin 1 (Sirt1)具有腎臟保護作用,然而,它在腎臟內的分佈及功能仍未清楚。吾人證實Sirt1在大鼠腎臟主要表現於腎小管及間質細胞的細胞質,且與aquaporin-2有共同位置,顯示它可能參與鈉與水的調節。大鼠禁食24小時後,其Sirt1在腎臟非腎絲球部分的細胞質內表現上升,但在大量飲水(每公斤體重50毫升)或禁止飲水24小時後,腎臟的Sirt1表現量並無改變。給予低鹽食物(0.075% NaCl)或限制60%的熱量攝取7天後,腎臟的Sirt1表現明顯增加;而攝取高鹽食物(8% NaCl)後,腎臟的Sirt1表現無明顯改變。攝取低鹽食物也會使心臟、肌肉、腦部及脂肪組織內Sirt1表現增加。低鹽時大鼠腎臟的飢餓素(ghrelin)表現量也增加,且與Sirt1的分佈型式相似。以集尿管細胞株的體外實驗發現,ghrelin增加Sirt1表現是藉由活化其受體而達成。這個結果指出此”ghrelin-Sirt1系統”可能參與調節遠端腎元的對鈉的重吸收。
另一方面,吾人以單側輸尿管阻塞(unilateral ureteral obstruction, UUO)為模式,探討Sirt1在腎臟發炎和纖維化的角色和機轉。Sirt1在阻塞側腎臟的腎小管及間質細胞表現上升,但在對側腎臟則無變化。Resveratrol是一種Sirt1活化劑,可減少阻塞側腎臟的發炎和纖維化,而Sirt1抑制劑sirtinol使發炎更厲害。此結果顯示Sirt1可能可預防腎小管間質的纖維化。進一步發現,阻塞側腎臟的血管收縮素第一型受體(angiotensin type 1 receptor, AT1R)、核因子活化B細胞κ輕鏈增強子(NF-κB), 單核球趨化蛋白-1 (MCP-1)和纖維連接蛋白(fibronectin)的表現增加,而Resveratrol可減少這些分子的表現量,反之,sirtinol加強這些分子的表現。在腎臟纖維母細胞的體外實驗,過度表現Sirt1會減少AT1R和NF-κB的表現,而減少Sirt1表現量則出現相反結果。Sirtinol會增加AT1R、NF-κB、MCP-1和結締組織生長因子的表現,而resveratrol則減少AT1R的表現。吾人的結果顯示Sirt1在纖維母細胞中抑制AT1R和NF-κB的表現,而此機制可能於Sirt1減少UUO引起傷害的現象中扮演重要角色。 | zh_TW |
dc.description.abstract | Sirtuin 1(Sirt1) is a nicotinamide adenine dinucleotide-dependent deacetylase known to be associated with many cellular activities. Previous studies have shown that Sirt1 is renoprotective; however, details regarding its distribution and functions in the kidney remain unknown. Our study demonstrated that Sirt1 was mainly expressed in the cytoplasm of tubulointerstitial cells in normal rat kidneys and was co-localized with aquaporin 2, indicating it may be involved in water/salt regulation. After a 24-h fast, renal Sirt1 expression increased in the non-glomerular cytoplasmic portion of the kidney. No significant changes in Sirt1 expression occurred after water loading (50 mL/kg) or 24-h water deprivation. After consuming a low-salt (0.075%) or 60% calorie restriction diet for 7 days, Sirt1 expression in the rat kidney was significantly increased, whereas a high-salt (8%) diet did not change the level of Sirt1 expression. The low-salt diet also increased Sirt1 expression in the heart, muscle, brain, and fat tissues. The increased Sirt1 that was observed in rats on a low-salt diet was associated with increased ghrelin expression in the distal nephron, with both molecules exhibiting similar distribution patterns. An in vitro experiment suggested that ghrelin increases Sirt1 expression in cortical collecting duct cells by activating ghrelin receptors. These results indicated that this ‘ghrelin-Sirt1 system’ may participate in regulating sodium reabsorption in the distal nephron.
On the other hand, we explored the roles and mechanisms of Sirt1 on renal inflammation and fibrosis by using unilateral ureteral obstruction (UUO) rat model. Sirt1 expression increased significantly in the obstructed kidney but not in the contralateral kidney and was mainly detected in tubulointerstitial cells. Resveratrol, a Sirt1 activator, decreased UUO-induced inflammation and fibrosis, while sirtinol, a Sirt1 inhibitor, enhanced UUO-induced inflammation. These results suggest that Sirt1 may prevent renal tubulointerstitial fibrosis. In vivo, we evaluated the effects of activating or inhibiting Sirt1 on renal pathology and UUO pathogenesis mediators; in vitro, we evaluated the effects of regulating Sirt1 expression or activity on UUO pathogenesis mediators in renal fibroblasts. UUO increased renal angiotensin type 1 receptor (AT1R), NF-κB, monocyte chemotactic protein 1 (MCP-1), and fibronectin expression. Resveratrol attenuated these UUO-induced changes, whereas sirtinol enhanced them, with the exception of fibronectin. In renal fibroblasts, Sirt1 overexpression reduced AT1R and NF-κB levels, while Sirt1 knockdown had the opposite effects. Sirtinol increased the levels of AT1R, NF-κB, MCP-1, and connective tissue growth factor, while resveratrol reduced AT1R levels. Our results suggested that Sirt1 inhibited AT1R and NF-κB expression in renal fibroblasts and that these mechanisms may play roles in alleviating UUO-induced damages. | en |
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dc.description.tableofcontents | 誌謝…………………………………………………………………………………. i
中文摘要……………………………………………………………………………. ii 英文摘要……………………………………………………………………………. iv 博士論文內容 第一章 緒論………………………………………………………………………….. 1 1.1 簡介…………………………………………………………………………... 1 1.2 酵母菌的Sir2到哺乳類的Sirt1:Sirtuins的歷史背景及文獻回顧….…… 1 1.2.1 Sirt1:限制熱量攝取使壽命延長的中介者………………………….. 2 1.2.2 Sirt1在細胞中的調控與角色…………………………………….…… 3 1.2.3 Sirt1對與老化相關疾病的保護作用…………………………….…… 3 1.2.4腎臟以外器官的疾病對於Sirt1表現的影響…………………….…... 6 1.3 Sirt1在腎臟的角色及生理意義……………………………………………… 7 1.3.1 限制熱量攝取或禁食對腎臟中Sirt1的表現可能產生影響…….….. 7 1.3.2 腎臟中Sirt1可能具有調節鈉或水代謝的生理意義………………... 8 1.4 Sirt1在腎臟疾病的角色及可能的臨床應用………………………………… 9 1.4.1 腎臟疾病對Sirt1表現的影響…………………………………...…… 9 1.4.2 調節Sirt1的表現量或活性對腎臟疾病的影響:機制探討………. 10 1.4.2.1 急性腎傷害的動物模式……………………………………... 10 1.4.2.2 慢性腎疾病的動物模式……………………………………... 11 1.4.2.3 關於腎臟纖維化的研究……………………………………... 12 1.4.2.4 其他腎臟疾病的動物模式或細胞研究……………...……… 14 1.4.3 Sirt1在與腎臟相關的疾病可能的臨床應用……………………..… 14 1.4.3.1 糖尿病腎病變……………………...………………………… 14 1.4.3.2 與發炎相關的腎病變………………………………………... 15 1.4.3.3 與缺血-再灌流相關的腎病變……………….………………. 15 1.4.3.4 腎臟纖維化的預防………………………………………...… 16 1.5 研究主題及其重要性和創新性……………………………………………. 16 1.5.1 Sirt1在腎臟的分佈………………………………………………….. 16 1.5.2 Sirt1在腎臟可能的生理角色研究………………………………….. 17 1.5.3 Sirt1在腎臟疾病病理中可能扮演的角色..………………………… 17 1.5.4 調節Sirt1的表現或活性保護腎臟的機制………………………… 18 1.6 研究假說及特定目的………………………………………………………. 19 1.6.1 Sirt1在腎臟的分佈不平均,且其分佈與其生理或病理角色有關.. 19 1.6.2 在腎臟生理壓力下,Sirt1可被調節以因應生理狀況的改變……. 19 1.6.3 在腎臟疾病狀態,Sirt1可被調節以應付改變……………………. 20 1.6.4 調節Sirt1的表現量或活性可改變腎臟疾病的進程……………… 20 第二章 研究方法與材料……………………………………………………..…….. 21 2.1實驗動物…………………………………………………………………..… 21 2.1.1 實驗動物品系及飼養…………………………..…………………… 21 2.1.2 生理壓力含禁食、7天限制熱量攝取、飲食中水及鹽分的改變... 21 2.1.3 單側輸尿管阻塞動物實驗模式………………………………...…... 22 2.2從腎組織分離出腎絲球…………………………………………………….. 23 2.3腎臟組織學分析…………………………………………………………….. 23 2.3.1 免疫組織化學染色………………………………………………….. 23 2.3.2 特殊染色及檢驗…………………………………………………….. 24 2.3.3 細胞凋亡染色分析(TUNEL Assay)………………………………… 25 2.4免疫螢光染色………………………….…………………………………….. 25 2.4.1 第一部份:不同腎臟節段之Sirt1表現及分佈分析………………. 25 2.4.2 第二部分:探討在UUO模式中增加的腎臟間質細胞為何……… 26 2.5核質分離……………………………….…………………………………….. 26 2.6西方墨點法………………………………………………….……………….. 27 2.6.1 第一部份:Sirt1的分佈與生理角色之研究……….………………. 27 2.6.2 第二部份:Sirt1在UUO中扮演之角色研究……..……………….. 28 2.7小鼠皮質集尿管細胞mpkCCD培養及處理……………….………………. 29 2.7.1 mpkCCD細胞培養…………………………………………...……… 29 2.7.2 mpkCCD細胞的藥物處理……………………………………...…… 29 2.8大鼠腎纖維母細胞NRK-49F細胞培養及處理…………………………… 29 2.8.1 NRK-49F細胞培養…………………………………………………... 29 2.8.2 增加和減少NRK-49F細胞內Sirt1的表現量……………………… 30 2.8.3 NRK-49F細胞的藥物處理……………………………………….….. 30 2.9核糖核酸萃取及Sirt1信使核糖核酸(mRNA)定量……………………...... 31 2.9.1 核糖核酸萃取……………………………………………………….. 31 2.9.2 定量即時聚合酶鏈鎖反應(Quantitative real-time PCR)…………… 31 2.9.3 逆轉錄聚合酶鏈鎖反應(RT-PCR)………………………………..… 31 2.10尿液及血漿的分析………………………………………………………..... 32 2.11統計方法…………………………………………………………………..... 32 第三章 結果…………………………….…………………………………….…….. 33 3.1 Sirt1在腎臟的分佈及表現………………………………………………….. 33 3.2 Sirt1在腎臟受到生理壓力之後的變化…………………………………….. 33 3.2.1 禁食24小時之後腎臟Sirt1表現量的變化………………………… 33 3.2.2 在大量飲水或禁止飲水之後腎臟Sirt1表現的變化………………. 34 3.2.3 限制熱量攝取,高鹽或低鹽飲食7天後腎臟Sirt1表現的變化…. 34 3.2.4 限制熱量攝取,高鹽或低鹽飲食7天後腎外Sirt1表現的變化…. 35 3.3 低鹽飲食與飢餓素(ghrelin)………………………………………………... 35 3.3.1 低鹽飲食增加腎內飢餓素,但限制熱量攝取不改變腎內飢餓素… 35 3.3.2 飢餓素經由飢餓素受器可增加Sirt1的表現………………………. 36 3.3.3 限制熱量攝取,高鹽或低鹽飲食7天後胃及腎外飢餓素的變化... 36 3.4 Sirt1在單側輸尿管阻塞模式(UUO)中的角色探討………………………... 36 3.4.1 單側輸尿管阻塞模式(UUO)中Sirt1表現量的變化……………….. 36 3.4.2 UUO增加腎小管、巨噬細胞及間質纖維母細胞的Sirt1表現量.… 37 3.4.3 UUO引致的發炎及纖維化反應被resveratrol及sirtinol改變…….. 38 3.4.4 UUO引致的細胞凋亡及氧化壓力被resveratrol及sirtinol改變….. 39 3.4.5 UUO引致的促發炎因子變化被resveratrol減弱而被sirtinol加強.. 39 3.4.6 NRK-49F細胞中Sirt1抑制第一型血管張力素II受體的表現........ 40 3.4.7 NRK-49F細胞中Sirt1抑制NF-κB的表現量……………………… 40 3.4.8 Sirt1對發炎及纖維化相關因子表現量的影響………………...…… 40 3.4.9 Sirt1對第二型血管張力素II受體表現無顯著影響………………... 41 第四章 討論……………………………………………………………………….... 42 4.1 Sirt1在腎臟生理意義的研究:分佈型式與生理意義的關係………….…. 42 4.2 可調節腎臟中Sirt1表現量的生理壓力…………………………………… 42 4.2.1 不同時間的禁食或限制熱量攝取對腎臟Sirt1表現的影響………. 42 4.2.2 大量飲水及禁止飲水對腎臟Sirt1表現的影響……………………. 43 4.2.3 攝取低鹽食物或高鹽食物對腎臟Sirt1表現的影響………………. 44 4.2.4 攝取低鹽食物或高鹽食物對腎以外組織Sirt1表現的影響…….… 44 4.3 Ghrelin-Sirt1 system在遠端腎元鈉調控可能的角色…………………….... 45 4.4 Sirt1生理意義研究待解決的問題………………………………………….. 48 4.5 Sirt1的病理意義:側重於對於UUO引致發炎及纖維化的角色………… 49 4.5.1 Sirt1在UUO引致腎臟發炎及纖維化的角色:生體研究…………. 50 4.5.2 Sirt1在UUO引致腎臟發炎及纖維化的角色:細胞研究…………. 55 4.6 Sirt1在腎臟病理意義待解決的問題……………………………………….. 57 4.6.1 Sirt1在UUO引致腎臟纖維化的角色:生體研究差異比較………. 57 4.6.2 不同腎臟細胞中UUO後Sirt1在腎臟纖維化的角色……………… 60 第五章 展望……………………………………………………………………….... 62 5.1 Sirt1在腎臟生理意義的展望……………………………………………….. 62 5.1.1 關於Sirt1在腎臟生理意義的研究可能對基礎的貢獻………….… 63 5.1.2 關於Sirt1在腎臟生理意義的研究可能對臨床的貢獻與應用….… 66 5.2 Sirt1在腎臟病理意義的展望……………………..………………………… 67 5.2.1 關於Sirt1在腎臟病理意義的研究可能對基礎的貢獻……………. 67 5.2.2 關於Sirt1在腎臟病理意義的研究可能對臨床的貢獻與應用……. 69 第六章 論文英文簡述(Summary)………………………………………………….. 72 參考文獻…………………………………………………………………………….... 84 圖表………………………………………………………………………………........ 95 附錄:個人在碩博士班修業期間所發表之相關論文清冊……………………….. 120 | |
dc.language.iso | zh-TW | |
dc.title | Sirt1在腎臟中生理及病理的角色 | zh_TW |
dc.title | The Physiologic and Pathologic Roles of Sirt1 in the Kidney | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-1 | |
dc.description.degree | 博士 | |
dc.contributor.coadvisor | 楊偉勛(Wei-Shiung Yang) | |
dc.contributor.oralexamcommittee | 辛錫璋,林琬琬,楊智偉 | |
dc.subject.keyword | Sirtuin 1,腎臟,飢餓素,單側輸尿管阻塞,腎臟纖維化,血管收縮素第一型受體,核因子活化B細胞κ輕鏈增強子, | zh_TW |
dc.subject.keyword | Sirtuin 1,Kidney,Ghrelin,Unilateral ureteral obstruction,Renal fibrosis,Angiotensin type 1 receptor,NF-κB, | en |
dc.relation.page | 120 | |
dc.identifier.doi | 10.6342/NTU201603860 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-12-30 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
顯示於系所單位: | 臨床醫學研究所 |
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