請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43331完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 康照洲(Jaw-Jou Kang) | |
| dc.contributor.author | I-Hsiu Liu | en |
| dc.contributor.author | 劉怡秀 | zh_TW |
| dc.date.accessioned | 2021-06-15T01:50:04Z | - |
| dc.date.available | 2016-10-07 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-15 | |
| dc.identifier.citation | Akintobi AM, Villano CM, White LA (2007) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure of normal human dermal fibroblasts results in AhR-dependent and -independent changes in gene expression. Toxicol Appl Pharmacol 220: 9-17.
Araya R, Kudo M, Kawano M, Ishii K, Hashikawa T, Iwasato T, Itohara S, Terasaki T, Oohira A, Mishina Y, Yamada M (2008) BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier. Mol Cell Neurosci 38: 417-430. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW (2002) Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 105: 1672-1678. Baird WM, Hooven LA, Mahadevan B (2005) Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action. Environ Mol Mutagen 45: 106-114. Benchabane H, Wrana JL (2003) GATA- and Smad1-dependent enhancers in the Smad7 gene differentially interpret bone morphogenetic protein concentrations. Mol Cell Biol 23: 6646-6661. Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL (1993) Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest 91: 1800-1809. Cacciola RR, Guarino F, Polosa R (2007) Relevance of endothelial-haemostatic dysfunction in cigarette smoking. Curr Med Chem 14: 1887-1892. Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438: 932-936. Chan MC, Nguyen PH, Davis BN, Ohoka N, Hayashi H, Du K, Lagna G, Hata A (2007) A novel regulatory mechanism of the bone morphogenetic protein (BMP) signaling pathway involving the carboxyl-terminal tail domain of BMP type II receptor. Mol Cell Biol 27: 5776-5789. Chang H, Brown CW, Matzuk MM (2002) Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 23: 787-823. Chen Q, Chen H, Zheng D, Kuang C, Fang H, Zou B, Zhu W, Bu G, Jin T, Wang Z, Zhang X, Chen J, Field LJ, Rubart M, Shou W, Chen Y (2009) Smad7 is required for the development and function of the heart. J Biol Chem 284: 292-300. Chen Z, Boreham J (2002) Smoking and cardiovascular disease. Semin Vasc Med 2: 243-252. Cogliano VJ, Baan RA, Straif K, Grosse Y, Secretan B, El Ghissassi F (2008) Use of mechanistic data in IARC evaluations. Environ Mol Mutagen 49: 100-109. Corriere MA, Rogers CM, Eliason JL, Faulk J, Kume T, Hogan BL, Guzman RJ (2008) Endothelial Bmp4 is induced during arterial remodeling: effects on smooth muscle cell migration and proliferation. J Surg Res 145: 142-149. Czernin J, Waldherr C (2003) Cigarette smoking and coronary blood flow. Prog Cardiovasc Dis 45: 395-404. David L, Feige JJ, Bailly S (2009) Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine Growth Factor Rev 20: 203-212. David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S (2007) Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood 109: 1953-1961. Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425: 577-584. Doi T, Puri P, Bannigan J, Thompson J (2011) BMPR1A-mediated BMP1 signalling is disrupted in the cadmium-induced omphalocele in the chick model. Pediatr Surg Int 27: 617-621. Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, Yuan JX, Deutsch R, Jamieson SW, Thistlethwaite PA (2003) Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 348: 500-509. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, Miyazono K (2001) Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem 276: 12477-12480. Eivers E, Fuentealba LC, De Robertis EM (2008) Integrating positional information at the level of Smad1/5/8. Curr Opin Genet Dev 18: 304-310. Freedman SB, Isner JM (2001) Therapeutic angiogenesis for ischemic cardiovascular disease. J Mol Cell Cardiol 33: 379-393. Galvin KM, Donovan MJ, Lynch CA, Meyer RI, Paul RJ, Lorenz JN, Fairchild-Huntress V, Dixon KL, Dunmore JH, Gimbrone MA, Jr., Falb D, Huszar D (2000) A role for smad6 in development and homeostasis of the cardiovascular system. Nat Genet 24: 171-174. Gaussin V, Van de Putte T, Mishina Y, Hanks MC, Zwijsen A, Huylebroeck D, Behringer RR, Schneider MD (2002) Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3. Proc Natl Acad Sci U S A 99: 2878-2883. Goldman DC, Donley N, Christian JL (2009) Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesis. Mech Dev 126: 117-127. Gong Z, Yang J, Yang M, Wang F, Wei Q, Tanguay RM, Wu T (2006) Benzo(a)pyrene inhibits expression of inducible heat shock protein 70 in vascular endothelial cells. Toxicol Lett 166: 229-236. Gramatzki D, Pantazis G, Schittenhelm J, Tabatabai G, Kohle C, Wick W, Schwarz M, Weller M, Tritschler I (2009) Aryl hydrocarbon receptor inhibition downregulates the TGF-beta/Smad pathway in human glioblastoma cells. Oncogene 28: 2593-2605. Guo X, Wang XF (2009) Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res 19: 71-88. Harrison RE, Berger R, Haworth SG, Tulloh R, Mache CJ, Morrell NW, Aldred MA, Trembath RC (2005) Transforming growth factor-beta receptor mutations and pulmonary arterial hypertension in childhood. Circulation 111: 435-441. Hassel S, Schmitt S, Hartung A, Roth M, Nohe A, Petersen N, Ehrlich M, Henis YI, Sebald W, Knaus P (2003) Initiation of Smad-dependent and Smad-independent signaling via distinct BMP-receptor complexes. J Bone Joint Surg Am 85-A Suppl 3: 44-51. Hernandez-Ochoa I, Karman BN, Flaws JA (2009) The role of the aryl hydrocarbon receptor in the female reproductive system. Biochem Pharmacol 77: 547-559. Hoffmann D, Djordjevic MV, Hoffmann I (1997) The changing cigarette. Prev Med 26: 427-434. Hong KH, Lee YJ, Lee E, Park SO, Han C, Beppu H, Li E, Raizada MK, Bloch KD, Oh SP (2008) Genetic ablation of the BMPR2 gene in pulmonary endothelium is sufficient to predispose to pulmonary arterial hypertension. Circulation 118: 722-730. Ichihara S, Yamada Y, Gonzalez FJ, Nakajima T, Murohara T, Ichihara G (2009) Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on the aryl hydrocarbon receptor. Biochem Biophys Res Commun 381: 44-49. Inoue Y, Imamura T (2008) Regulation of TGF-beta family signaling by E3 ubiquitin ligases. Cancer Sci 99: 2107-2112. Ishida W, Hamamoto T, Kusanagi K, Yagi K, Kawabata M, Takehara K, Sampath TK, Kato M, Miyazono K (2000) Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter. J Biol Chem 275: 6075-6079. Jaffe EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52: 2745-2756. Jeon HS, Dracheva T, Yang SH, Meerzaman D, Fukuoka J, Shakoori A, Shilo K, Travis WD, Jen J (2008) SMAD6 contributes to patient survival in non-small cell lung cancer and its knockdown reestablishes TGF-beta homeostasis in lung cancer cells. Cancer Res 68: 9686-9692. Juan SH, Lee JL, Ho PY, Lee YH, Lee WS (2006) Antiproliferative and antiangiogenic effects of 3-methylcholanthrene, an aryl-hydrocarbon receptor agonist, in human umbilical vascular endothelial cells. Eur J Pharmacol 530: 1-8. Kim HJ, Chung H, Yoo YG, Kim H, Lee JY, Lee MO, Kong G (2007) Inhibitor of DNA binding 1 activates vascular endothelial growth factor through enhancing the stability and activity of hypoxia-inducible factor-1alpha. Mol Cancer Res 5: 321-329. Kleinman HK, McGarvey ML, Liotta LA, Robey PG, Tryggvason K, Martin GR (1982) Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochemistry 21: 6188-6193. Knaus P, Sebald W (2001) Cooperativity of binding epitopes and receptor chains in the BMP/TGFbeta superfamily. Biol Chem 382: 1189-1195. Koenig BB, Cook JS, Wolsing DH, Ting J, Tiesman JP, Correa PE, Olson CA, Pecquet AL, Ventura F, Grant RA, et al. (1994) Characterization and cloning of a receptor for BMP-2 and BMP-4 from NIH 3T3 cells. Mol Cell Biol 14: 5961-5974. Korashy HM, El-Kadi AO (2006) The role of aryl hydrocarbon receptor in the pathogenesis of cardiovascular diseases. Drug Metab Rev 38: 411-450. Kozawa O, Matsuno H, Uematsu T (2001) Involvement of p70 S6 kinase in bone morphogenetic protein signaling: vascular endothelial growth factor synthesis by bone morphogenetic protein-4 in osteoblasts. J Cell Biochem 81: 430-436. Kretzschmar M, Doody J, Massague J (1997) Opposing BMP and EGF signalling pathways converge on the TGF-beta family mediator Smad1. Nature 389: 618-622. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA, 3rd, Loyd JE, Nichols WC, Trembath RC (2000) Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 26: 81-84. Langenfeld EM, Langenfeld J (2004) Bone morphogenetic protein-2 stimulates angiogenesis in developing tumors. Mol Cancer Res 2: 141-149. Lehmann K, Seemann P, Stricker S, Sammar M, Meyer B, Suring K, Majewski F, Tinschert S, Grzeschik KH, Muller D, Knaus P, Nurnberg P, Mundlos S (2003) Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2. Proc Natl Acad Sci U S A 100: 12277-12282. Li CH, Cheng YW, Hsu YT, Hsu YJ, Liao PL, Kang JJ (2010) Benzo[a]pyrene inhibits angiogenic factors-induced alphavbeta3 integrin expression, neovasculogenesis, and angiogenesis in human umbilical vein endothelial cells. Toxicol Sci 118: 544-553. Li ZD, Liu LZ, Shi X, Fang J, Jiang BH (2007) Benzo[a]pyrene-3,6-dione inhibited VEGF expression through inducing HIF-1alpha degradation. Biochem Biophys Res Commun 357: 517-523. Lonn P, Moren A, Raja E, Dahl M, Moustakas A (2009) Regulating the stability of TGFbeta receptors and Smads. Cell Res 19: 21-35. Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K, Benezra R (1999) Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401: 670-677. Massague J, Seoane J, Wotton D (2005) Smad transcription factors. Genes Dev 19: 2783-2810. Masterson JC, Molloy EL, Gilbert JL, McCormack N, Adams A, O'Dea S (2011) Bone morphogenetic protein signalling in airway epithelial cells during regeneration. Cell Signal 23: 398-406. Michaud SE, Menard C, Guy LG, Gennaro G, Rivard A (2003) Inhibition of hypoxia-induced angiogenesis by cigarette smoke exposure: impairment of the HIF-1alpha/VEGF pathway. FASEB J 17: 1150-1152. Miyazono K, Kamiya Y, Morikawa M (2010) Bone morphogenetic protein receptors and signal transduction. J Biochem 147: 35-51. Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16: 251-263. Murakami G, Watabe T, Takaoka K, Miyazono K, Imamura T (2003) Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Mol Biol Cell 14: 2809-2817. Murakami K, Mathew R, Huang J, Farahani R, Peng H, Olson SC, Etlinger JD (2010) Smurf1 ubiquitin ligase causes downregulation of BMP receptors and is induced in monocrotaline and hypoxia models of pulmonary arterial hypertension. Exp Biol Med (Maywood) 235: 805-813. Nakaoka T, Gonda K, Ogita T, Otawara-Hamamoto Y, Okabe F, Kira Y, Harii K, Miyazono K, Takuwa Y, Fujita T (1997) Inhibition of rat vascular smooth muscle proliferation in vitro and in vivo by bone morphogenetic protein-2. J Clin Invest 100: 2824-2832. Naruse M, Otsuka E, Ishihara Y, Miyagawa-Tomita S, Hagiwara H (2004) Inhibition of osteoclast formation by 3-methylcholanthrene, a ligand for arylhydrocarbon receptor: suppression of osteoclast differentiation factor in osteogenic cells. Biochem Pharmacol 67: 119-127. Nickel J, Sebald W, Groppe JC, Mueller TD (2009) Intricacies of BMP receptor assembly. Cytokine Growth Factor Rev 20: 367-377. Nicosia RF, and Ottinetti, A. (1990) Modulation of microvascular growth and morphogenesis by reconstituted basement membrane gel in three-dimensional cultures of rat aorta: a comparative study of angiogenesis in matrigel, collagen, fibrin, and plasma clot. . In Vitro Cell Dev Biol 26, 119-128. Nicosia RF, Ottinetti A (1990) Modulation of microvascular growth and morphogenesis by reconstituted basement membrane gel in three-dimensional cultures of rat aorta: a comparative study of angiogenesis in matrigel, collagen, fibrin, and plasma clot. In Vitro Cell Dev Biol 26: 119-128. Nishiyama K, Takaji K, Kataoka K, Kurihara Y, Yoshimura M, Kato A, Ogawa H, Kurihara H (2005) Id1 gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis. Circulation 112: 2840-2850. Nohe A, Hassel S, Ehrlich M, Neubauer F, Sebald W, Henis YI, Knaus P (2002) The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J Biol Chem 277: 5330-5338. Norton JD, Deed RW, Craggs G, Sablitzky F (1998) Id helix-loop-helix proteins in cell growth and differentiation. Trends Cell Biol 8: 58-65. Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (2000) Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A 97: 2626-2631. Owens EO, Toborek M, Hennig B (2009) Flavonoids protect against intercellular adhesion molecule-1 induction by benzo[a]pyrene. Bull Environ Contam Toxicol 83: 4-7. Park C, Lavine K, Mishina Y, Deng CX, Ornitz DM, Choi K (2006) Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation. Development 133: 3473-3484. Patil AJ GA, Sharma A, Chwa M, Seigel GM, Kuppermann BD, Kenney MC. (2009) Effects of benzo(e)pyrene on the retinal neurosensory cells and human microvascular endothelial cells in vitro. Curr Eye Res 34(8):672-82. Peter Guengerich F, Chun YJ, Kim D, Gillam EM, Shimada T (2003) Cytochrome P450 1B1: a target for inhibition in anticarcinogenesis strategies. Mutat Res 523-524: 173-182. Puga A, Ma C, Marlowe JL (2009) The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways. Biochem Pharmacol 77: 713-722. Puranik R, Celermajer DS (2003) Smoking and endothelial function. Prog Cardiovasc Dis 45: 443-458. Raida M, Clement JH, Leek RD, Ameri K, Bicknell R, Niederwieser D, Harris AL (2005) Bone morphogenetic protein 2 (BMP-2) and induction of tumor angiogenesis. J Cancer Res Clin Oncol 131: 741-750. Raida M, Heymann AC, Gunther C, Niederwieser D (2006) Role of bone morphogenetic protein 2 in the crosstalk between endothelial progenitor cells and mesenchymal stem cells. Int J Mol Med 18: 735-739. Ramoshebi LN, Ripamonti U (2000) Osteogenic protein-1, a bone morphogenetic protein, induces angiogenesis in the chick chorioallantoic membrane and synergizes with basic fibroblast growth factor and transforming growth factor-beta1. Anat Rec 259: 97-107. Reddi AH (2001) Interplay between bone morphogenetic proteins and cognate binding proteins in bone and cartilage development: noggin, chordin and DAN. Arthritis Res 3: 1-5. Roman BL, Pham VN, Lawson ND, Kulik M, Childs S, Lekven AC, Garrity DM, Moon RT, Fishman MC, Lechleider RJ, Weinstein BM (2002) Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels. Development 129: 3009-3019. Ross S, Hill CS (2008) How the Smads regulate transcription. Int J Biochem Cell Biol 40: 383-408. Rothhammer T, Bataille F, Spruss T, Eissner G, Bosserhoff AK (2007) Functional implication of BMP4 expression on angiogenesis in malignant melanoma. Oncogene 26: 4158-4170. Sakurai D, Tsuchiya N, Yamaguchi A, Okaji Y, Tsuno NH, Kobata T, Takahashi K, Tokunaga K (2004) Crucial role of inhibitor of DNA binding/differentiation in the vascular endothelial growth factor-induced activation and angiogenic processes of human endothelial cells. J Immunol 173: 5801-5809. Sapkota G, Alarcon C, Spagnoli FM, Brivanlou AH, Massague J (2007) Balancing BMP signaling through integrated inputs into the Smad1 linker. Mol Cell 25: 441-454. Savouret JF, Berdeaux A, Casper RF (2003) The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases. Nutr Metab Cardiovasc Dis 13: 104-113. Shields PG, Bowman ED, Harrington AM, Doan VT, Weston A (1993) Polycyclic aromatic hydrocarbon-DNA adducts in human lung and cancer susceptibility genes. Cancer Res 53: 3486-3492. Shimasaki S, Moore RK, Otsuka F, Erickson GF (2004) The bone morphogenetic protein system in mammalian reproduction. Endocr Rev 25: 72-101. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS (2006) A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38: 525-527. Simic P, Vukicevic S (2007) Bone morphogenetic proteins: from developmental signals to tissue regeneration. Conference on bone morphogenetic proteins. EMBO Rep 8: 327-331. Sorescu GP, Sykes M, Weiss D, Platt MO, Saha A, Hwang J, Boyd N, Boo YC, Vega JD, Taylor WR, Jo H (2003) Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response. J Biol Chem 278: 31128-31135. Stabile H, Mitola S, Moroni E, Belleri M, Nicoli S, Coltrini D, Peri F, Pessi A, Orsatti L, Talamo F, Castronovo V, Waltregny D, Cotelli F, Ribatti D, Presta M (2007) Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor. Blood 109: 1834-1840. Suzuki Y, Montagne K, Nishihara A, Watabe T, Miyazono K (2008) BMPs promote proliferation and migration of endothelial cells via stimulation of VEGF-A/VEGFR2 and angiopoietin-1/Tie2 signalling. J Biochem 143: 199-206. Topper JN, Cai J, Qiu Y, Anderson KR, Xu YY, Deeds JD, Feeley R, Gimeno CJ, Woolf EA, Tayber O, Mays GG, Sampson BA, Schoen FJ, Gimbrone MA, Jr., Falb D (1997) Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc Natl Acad Sci U S A 94: 9314-9319. Urness LD, Sorensen LK, Li DY (2000) Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet 26: 328-331. Valdimarsdottir G, Goumans MJ, Rosendahl A, Brugman M, Itoh S, Lebrin F, Sideras P, ten Dijke P (2002) Stimulation of Id1 expression by bone morphogenetic protein is sufficient and necessary for bone morphogenetic protein-induced activation of endothelial cells. Circulation 106: 2263-2270. van Hinsbergh VW, Collen A, Koolwijk P (2001) Role of fibrin matrix in angiogenesis. Ann N Y Acad Sci 936: 426-437. Vayssier-Taussat M, Camilli T, Aron Y, Meplan C, Hainaut P, Polla BS, Weksler B (2001) Effects of tobacco smoke and benzo[a]pyrene on human endothelial cell and monocyte stress responses. Am J Physiol Heart Circ Physiol 280: H1293-1300. Voronov I, Heersche JN, Casper RF, Tenenbaum HC, Manolson MF (2005) Inhibition of osteoclast differentiation by polycyclic aryl hydrocarbons is dependent on cell density and RANKL concentration. Biochem Pharmacol 70: 300-307. West J, Harral J, Lane K, Deng Y, Ickes B, Crona D, Albu S, Stewart D, Fagan K (2008) Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions. Am J Physiol Lung Cell Mol Physiol 295: L744-755. Willette RN, Gu JL, Lysko PG, Anderson KM, Minehart H, Yue T (1999) BMP-2 gene expression and effects on human vascular smooth muscle cells. J Vasc Res 36: 120-125. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA (1988) Novel regulators of bone formation: molecular clones and activities. Science 242: 1528-1534. Wrighton KH, Lin X, Feng XH (2009) Phospho-control of TGF-beta superfamily signaling. Cell Res 19: 8-20. Xu L, Massague J (2004) Nucleocytoplasmic shuttling of signal transducers. Nat Rev Mol Cell Biol 5: 209-219. Yang X, Castilla LH, Xu X, Li C, Gotay J, Weinstein M, Liu PP, Deng CX (1999) Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126: 1571-1580. Yeh LC, Lee JC (1999) Osteogenic protein-1 increases gene expression of vascular endothelial growth factor in primary cultures of fetal rat calvaria cells. Mol Cell Endocrinol 153: 113-124. Zebedee Z, Hara E (2001) Id proteins in cell cycle control and cellular senescence. Oncogene 20: 8317-8325. Zhang F, Qiu T, Wu X, Wan C, Shi W, Wang Y, Chen JG, Wan M, Clemens TL, Cao X (2009) Sustained BMP signaling in osteoblasts stimulates bone formation by promoting angiogenesis and osteoblast differentiation. J Bone Miner Res 24: 1224-1233. Zhang H, Bradley A (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122: 2977-2986. Zhang YJ, Weksler BB, Wang L, Schwartz J, Santella RM (1998) Immunohistochemical detection of polycyclic aromatic hydrocarbon-DNA damage in human blood vessels of smokers and non-smokers. Atherosclerosis 140: 325-331. Zhu H, Kavsak P, Abdollah S, Wrana JL, Thomsen GH (1999) A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 400: 687-693. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43331 | - |
| dc.description.abstract | Benzo[a]pyrene (B[a]P), one of the polycyclic aromatic hydrocarbons family (PAHs), is a common environmental pollutant from cigarette smoke, charbroiled food, industrial combustion products and diesel exhaust. Emerging evidence showed that PAHs cause cardiovascular disease (CVD). Epidemiological studies indicate that smoking is responsible for one third of all CVD deaths, and each cigarette contains 19-50 ng B[a]P. Thus, exposure to B[a]P is associated with high risk CVD. In physiology, angiogenesis is thought to be a defense mechanism which protects tissue from ischemia. However, our previous studies showed that exposure to B[a]P could inhibit angiogenesis and the mechanisms need to be further investigated.
Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily involved in development, differention, cancer and angiogenesis. Abnormal BMP signaling may cause different CVD, therefore our aim is to investigate whether BMP signaling is involved in B[a]P-inhibited angiogenesis. We found that B[a]P could decrease the protein expression of BMP receptor 1A (BMPR1A), Id-1 and the level of Smad1/5 phosphorylation in a dose- and time-dependent manner. Moreover, B[a]P could decrease tube formation in HUVECs. Nevertheless, B[a]P treatment did not alter the mRNA expression of BMPR1A which indicated that B[a]P inhibited BMP signaling may be through post-translational modifications. By employing aryl hydrocarbon receptor (AhR) antagonist, | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T01:50:04Z (GMT). No. of bitstreams: 1 ntu-100-R98447010-1.pdf: 1780033 bytes, checksum: c73b69672e8f3df8471f2a483d147aa3 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 縮寫表(Abbreviations) ……………………………….………………………………...iv
圖表目錄(Figures and Tables) ……………………………………………………….....v 中文摘要…………………………………………….….……………………………....vi 英文摘要………………………………..……………….…………………………….viii 第一章 緒論 ( Introduction ) 1.1 苯芘 ( benzo[a]pyrene, B[a]P ) 毒理背景介紹….…………………………...……1 1.2 苯芘 ( B[a]P ) 與血管新生之相關性…………...…. …………………………….2 1.3 骨型態發生蛋白訊息傳遞 ( Bone Morphogenetic Protein, BMP signaling )...........3 1.4 骨型態發生蛋白訊息傳遞 ( BMP signaling ) 與心血管疾病之關係…..…...........5 1.5 骨型態發生蛋白訊息路徑 ( BMP signaling ) 與血管新生之調控……….………6 1.6 研究動機………………………………………………………………….………...8 第二章 實驗材料與方法 ( Materials and Methods ) 2.1 實驗材料…..……………….…………………………………………….……......10 2.1.1 實驗藥品與試劑…..……………….……………………………….…..…….......10 2.1.2 抗體 ( Antibodies )…………………………….. ……………………..….…….11 2.1.3 質體 ( Plasmids )………………………………………………………..…........12 2.2.1 人類臍靜脈內皮細胞 ( Human Umbilical Vein Endothelial Cells, HUVECs ) 之 分離與培養……………………………………………….…………….….........12 2.2.2 細胞毒性測試 ( Cell viability test/ MTT assay ) …….……………….....……..13 2.2.3 細胞萃取液收集 ( Cell lysate collection )……………………………………...13 2.2.4 西方墨點法 ( Western blot analysis )…….…………………...…….…..............14 2.2.5 管狀形成實驗 ( Tube formation assay )…….………………………….............14 2.2.6 細胞RNA萃取 ( RNA extraction ) …….………………………….…...............15 2.2.7 反轉錄-聚合酶連鎖反應 ( Reverse Transcription Polymerase Chain Reaction, RT-PCR )...............................................................................................15 2.2.8 慢病毒製備與感染 ( Lentivirus production and infection ) ………...…............16 2.2.9 統計分析 ( Statistic analysis )…….…………….…………………....…............17 第三章 實驗結果 ( Results ) 3.1 苯芘 ( B[a]P ) 處理下不會對人類臍靜脈內皮細胞產生細胞毒性…................18 3.2 苯芘能抑制人類臍靜脈內皮細胞之Smad1/5 磷酸化 …….…….......….............18 3.3 苯芘能抑制人類臍靜脈內皮細胞之inhibitor of DNA binding 1 ( Id-1 ) 蛋白表 現………………………………………………………………...…………………19 3.4 苯芘能抑制人類臍靜脈內皮細胞管狀構造形成作用……….……………...........20 3.5 苯芘能抑制人類臍靜脈內皮細胞之骨型態發生蛋白受體 ( Bone Morphogenetic Protein Receptor 1A, BMPR1A ) 蛋白表現…….……………….…….….............21 3.6α-NF 無法回復苯芘所抑制之骨型態發生蛋白訊息路徑 ( BMP signaling )…...22 3.7 AhR shRNA 無法回復苯芘所抑制之骨型態發生蛋白訊息路徑 ( BMP signaling )……………………………………………………………………..........23 3.8 苯芘會促進Smad6蛋白表現 …….………………………….…............................24 3.9 Smad6 shRNA 可以回復苯芘所抑制之管狀構造形成 ………….........................24 3.10 苯芘透過Smad6抑制BMP訊息傳遞…….……………………………..............25 第四章 討論 ( Discussion ) 4.1 苯芘抑制BMPR1A蛋白表現量而不影響mRNA表現量之探討……….............26 4.2 苯芘抑制Smad1/5 磷酸化之機制探討...................................................................27 4.3 Smad6 shRNA 可以回復苯芘所抑制血管新生作用之機制探討………………...28 4.4 苯芘抑制BMP訊息傳遞下游基因Id-1 蛋白表現與血管新生之關係…..…..….30 4.5 苯芘 ( B[a]P ) 處理抑制HUVECs 中BMP 訊息傳遞並非透過多環芳香烴受體 ( AhR )…….…………………………………………………….………..………31 4.6 苯芘抑制血管新生與BMP訊息傳遞之其他可能機制.........................................32 第五章 結論 (Conclusion) ...……................................................................................34 參考文獻 (References) ………......................................................................................35 圖表集 (Figures and Tables) .........................................................................................47 | |
| dc.language.iso | zh-TW | |
| dc.subject | 血管新生 | zh_TW |
| dc.subject | 人類臍靜脈內皮細胞 | zh_TW |
| dc.subject | 苯芘 | zh_TW |
| dc.subject | 骨型態發生蛋白 | zh_TW |
| dc.subject | angiogenesis | en |
| dc.subject | Human Umbilical Vein Endothelial Cells (HUVECs) | en |
| dc.subject | Benzo[a]pyrene (B[a]P) | en |
| dc.subject | Bone Morphogenetics Protein (BMP) | en |
| dc.title | 苯芘抑制血管新生之影響:骨型態發生蛋白訊息傳遞角色之探討 | zh_TW |
| dc.title | Inhibitory Effects of Benzo[a]pyrene on Angiogenesis: The Role of Bone Morphogenetic Protein Signaling | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 彭福佐,李珍珍 | |
| dc.subject.keyword | 苯芘,人類臍靜脈內皮細胞,血管新生,骨型態發生蛋白, | zh_TW |
| dc.subject.keyword | Benzo[a]pyrene (B[a]P),Human Umbilical Vein Endothelial Cells (HUVECs),angiogenesis,Bone Morphogenetics Protein (BMP), | en |
| dc.relation.page | 61 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-15 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| 顯示於系所單位： | 毒理學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-100-1.pdf 未授權公開取用 | 1.74 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。