成功大學博碩士論文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	楊皓安 Yang, Diane
論文名稱：	探討KLF10調控COX-1在血管內皮細胞之功能與特性 Functional characterization of KLF10 signaling-modulated gene, COX-1, in endothelial cells
指導教授：	王建平 Wang, Jiann-Ping
學位類別：	碩士 Master
系所名稱：	生物科學與科技學院 - 生命科學系 Department of Life Sciences
論文出版年：	2012
畢業學年度：	100
語文別：	英文
論文頁數：	48
中文關鍵詞：	血管新生、內皮細胞、環氧合酶-1
外文關鍵詞：	KLF10, COX-1, Angiogenesis
相關次數：	點閱：83 下載：1
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

Krüppel-like family (KLF) 為一群含有鋅指 (zinc finger) 結構的轉錄因子，並藉與目標基因啟動子直接結合的機制調控其轉錄，進而恆定許多重要的生理功能如生長發育、細胞分化及血管生成等。KLF家族中的成員之一，KLF10，已知在 TGF-beta 的訊息傳遞路徑中扮演著重要的角色。近來研究指出 KLF10 在 TGF-beta 的刺激下調控骨髓中 pro-angiogenic cells (PAC) 的分化，分化後的 PAC再藉由體內循環到組織受傷處進行血管新生以修復傷口；另一方面 KLF10 的基因剔除小鼠在上肢缺血手術實驗 (hindlimb ischemia) 後無法藉由血管新生回復被截斷的血流。此外 KLF10 的基因剔除小鼠於 Matrigel plug assay 顯示明顯的血管新生缺陷。這些新發現皆顯示KLF10參與在血管生成的過程中，但 KLF10 所涉及的血管新生成路徑仍尚未明瞭。
試驗以染色體免疫沉澱晶片 (ChIP-chip) 分析可能受 KLF10 調控的下游基因，其中環氧合酶-1 [cyclooxygenase 1 (COX-1; prostaglandin - endoperoxide synthase 1; PTGS1)] 為 KLF10 為眾目標基因之一。本論文陸續以啟動子活性分析(promoter activity assay)、電泳遷移率實驗 (electrophoretic mobility shift assay ; EMSA) 及染色質免疫共沉澱與聚合酶鏈鎖反應 (ChIP-PCR) 等實驗，先行確認了KLF10/COX-1 兩者間的調控關係，結果顯示 KLF10 可藉由結合到 COX-1 基因啟動子之 Sp/KLF 結合序列，以活化 COX-1 起動子轉錄。COX-1 在一般細胞中已知可催化前列腺素的生成反應，在血管內皮細胞能促使其進行血管新生，而在血小板則催化花生四烯酸 (arachidonic acid, AA) 所引起的血小板凝集。由反轉錄聚合酶鏈鎖反應 (RT-PCR) 與西方墨點染色法 (Western blot) 結果證實 KLF10 調控血管內皮細胞 COX-1 mRNA及蛋白質的表現。此外，為了深入探討 KLF10 所造成的影響是否也會反映在 COX-1 的功能上，論文再利用人類血管內皮細胞以細管形成試驗 (tube formation assay) 來評估血管新生；由結果發現在大量表現 KLF10 的基因轉染血管內皮細胞較控制組更快速並形成更多的血管管狀結構，此結果可被 COX-1 選擇性抑制劑 valeryl salicylate (VSA) 所壓抑。論文最後分析，KLF10 基因剃除鼠血小板亦如推測其凝集能力較正常小鼠者來的差。綜合上述的結果，KLF10 可藉由調控 COX-1 的表現量來進一步促使血管新生成以及血小板凝集。

TGF-beta is a vital cytokine known to participate in vascular formation and angiogenesis processes by modulating its several downstream factors. One of the TGF-beta inducible gene, Krüppel-like factor 10 (KLF10), is a zinc-finger transcription factors which play key regulatory roles in cellular growth, development, differentiation etc. Recent study has shown that KLF10 is involved in the process of angiogenesis by acting as a key transcriptional regulator of TGF-beta1 in pro-angiogenic cells (PAC) differentiation and function. KLF10–/– mice also displayed impaired blood flow recovery after hindlimb ischemia. However, the mechanism of KLF10 induced angiogenesis is still not well understood. From our ChIP-chip result, which have been adopt to elucidate the novel target genes and signaling cascades of KLF10, cyclooxygenase 1 (COX-1; prostaglandin-endoperoxide synthase 1; PTGS1) was identified to be one of the target genes that may be regulated by KLF10 through direct promoter binding. In order to investigate the function of KLF10/COX-1 axis, promoter activity, EMSA, ChIP-PCR, tube formation assays and platelet aggregation assays were serially performed. Using luciferase reporter assays, KLF10 was found to activate COX-1 promoter activity when overexpressed KLF10 in both endothelial cells: bEnd-3 and HUVEC. In the same experiment, the expression levels of COX-1 mRNA and protein were up-regulated by KLF10 transfected. It is known that COX-1 is the key enzyme in prostaglandin biosynthesis which further regulated angiogenesis in endothelial cells. In tube formation assay, KLF10 overexpressed endothelial cells formed organized tube-like structure better than in contrast to the control group. This KLF10-induced tube formation could be repressed by COX-1 selected inhibitor- valeryl salicylate. Moreover, KLF10-deficient mice perform weaker arachidonic acid-induced platelet aggregation. In sum, these results indicate an important role for KLF10 in angiogenesis and platelet aggregation through the activation of COX-1.

誌謝	I
中文摘要	II
Abstract	IV
Contents	VI
Figure Contents	IX
Chapter 1	1
Introduction	1
1.1	Angiogenesis	1
1.1.1	Process of angiogenesis	1
1.2	TGF-beta signaling	1
1.2.1  Role of TGF-beta in angiogenesis	2
1.2.2  TGF-beta is involved in atherosclerosis	3
1.3	Krüpple like factors	3
1.3.1  Regulators of KLF10	4
1.3.2  Functions of KLF10	4
1.3.3  KLF10 participates in angiogenesis process	5
1.3.4  KLF10 is involved in multiple diseases	6
1.4 Physiological function of COX-1	6
1.4.1  Regulators of COX-1	7
1.4.2  COX-1 is involved in many diseases	8
1.5 Aims	9
Chapter 2	10
Materials and Methods	10
2.1	Cell culture	10
2.2	Plasmid construction	10
2.3	Transient transfection	11
2.4	Preparation of nuclear extracts	12
2.5	EMSA (Electrophoretic Mobility Shift Assay)	12
2.6	ChIP-PCR assays (Chromosome Immunoprecipitation PCR assays)	13
2.7	Dual-luciferase assay	14
2.8	Protein extraction	14
2.9	Western blotting	15
2.10	Reverse transcription PCR	15
2.11	Tube formation assay	16
2.12	Platelets aggregation assay	16
Chapter 3	18
Results	18
3.1	KLF10 interacts with COX-1 promoter by binding to specific Sp/KLF sequence.	18
3.1.1	COX-1 promoter as a possible target of KLF10	18
3.1.2	KLF10 forms a protein-DNA complex in COX-1 promoter region	18
3.1.3	KLF10 binding to COX-1 proximal Sp/KLF binding sequence	19
3.2	COX-1 transcription could be activated by TGF-beta	19
3.2.1  Construction of COX-1 promoter to pGL3 Luciferase Reporter Vector	19
3.2.2	TGF-beta activates COX-1 transcription	19
3.3	COX-1 promoter activities were activated by KLF10	20
3.3.1	KLF10 could active COX-1 promoter but not site-mutant promoter construct	20
3.3.2  KLF10 phosphrylation sites are all vital for COX-1 transcriptinal activation.	20
3.4 KLF10 modulates COX-1 expression in endothelial cells	20
3.4.1  Important function of COX-1 in endotheilal cells	20
3.4.2  COX-1 promoter activities increase with KLF10 level	21
3.4.3  Proximal Sp/KLF binding site is critical for COX-1 transcription activation	21
3.4.4  KLF10 modulates COX-1 protein expression	21
3.5 KLF10 enhances tube formation through COX-1 activation	22
3.5.1  KLF10 modulates mRNA and protein expression of COX-1 in HUVEC	22
3.5.2  HUVEC forms tube-like structure when overexpressed KLF10	22
3.6 Less extent of platelet aggregation in KLF10 knockout mice	23
Chapter 4	24
Discussion	24
4.1	KLF10 regulates COX-1 through binding Sp/KLF binding site	24
4.2	KLF10 as an activator in transcription regulation	24
4.3	Competition binding of Sp/KLF family protein in DNA	25
4.4	TGF-beta and estrogen as regulator of COX-1	25
4.5	Angiogenic switch regulated by TGF-beta	26
4.6	KLF10 enhances angiogenesis by modulating COX-1	27
4.7	TGF-beta might enhance angiogenesis by modulate KLF10/COX-1 axis.	27
4.8	Loss of KLF10 reduces arachidonic acid-induced platelet aggregation	28
Chapter 5	30
Conclusion	30
References	31




 
Figure Contents

Figure 1. KLF10 directly bind to COX-1 promoter through a serial assays including ChIP-chip, EMSA and ChIP-PCR.	41
Figure 2. COX-1 transcription activities could be activated by TGF-beta.	42
Figure 3. KLF10 directly bind to COX-1 promoter and further regulate its transcriptional activity.	43
Figure 4. Transcriptional and translational level analysis of COX-1 in KLF10 transfected mouse endothelial cells, bEnd.3.	44
Figure 5. Transcriptional and translational level analysis of COX-1 in KLF10 transfected human endothelial cells, HUVECs.	45
Figure 6. Images analysis of tube formation assay in human endothelial cells.	46
Figure 7. Comparison and quantification the phenomena of tube formation assay in different treatments.	47
Figure 8. Comparison the platelet aggregation between wild type and KLF10 gene deficient mice.	48

                                    

Alfranca, A., López-Oliva, J., Genís, L., López-Maderuelo, D., Mirones, I., Salvado, D., et al. (2007). PGE2 induces angiogenesis via MT1-MMP−mediated activation of the TGF β /Alk5 signaling pathway. Blood, 112(4), 1120-1128.

Awtry, E. H., & Loscalzo, J. (2000). Aspirin Circulation. , 101, 1206-1218.

Bensamoun, S. F., Hawse, J. R., Subramaniam, M., Ilharreborde, B., Bassillais, A., Benhamou, C. L., et al. (2006). TGFbeta inducible early gene-1 knockout mice display defects in bone strength and microarchitecture. Bone, 39(6), 1244-1251.

Bertolino, P., Deckers, M., Lebrin, F., & ten Dijke, P. (2005). Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest, 128(6 Suppl), 585S-590S.

Bieker, J. J. (2001). Kruppel-like factors: three fingers in many pies. [Review]. J Biol Chem, 276(37), 34355-34358.

Bobik, A., Agrotis, A., Kanellakis, P., Dilley, R., Krushinsky, A., Smirnov, V., et al. (1999). Distinct patterns of transforming growth factor-beta isoform and receptor expression in human atherosclerotic lesions. Colocalization implicates TGF-beta in fibrofatty lesion development. Circulation, 99(22(22), 2883-2891.

Botting, R. (2006). Inhibitors of cyclooxygenases: mechanisms, selectivity and uses. J Physiol Pharmacol. , 57(5), 113-124.

Bryant, C., Appleton, I., & Mitchell, J. (1998). Vascular endothelial growth factor upregulates constitutive cyclooxygenase 1 in primary bovine and human endothelial cells. Life Sci. , 62(24), 2195-2201.

Camitta, M. G. W., Gabel, S. A., Chulada, P., Bradbury, J. A., Langenbach, R., Zeldin, D. C., et al. (2001). Cyclooxygenase-1 and -2 Knockout Mice Demonstrate Increased Cardiac Ischemia/Reperfusion Injury but Are Protected by Acute Preconditioning. Circulation, 104(20), 2453-2458.

Cao, Z., Wara, A. K., Icli, B., Sun, X., Packard, R. R., Esen, F., et al. (2009). Kruppel-like factor KLF10 targets transforming growth factor-beta1 to regulate CD4(+)CD25(-) T cells and T regulatory cells. J Biol Chem, 284(37), 24914-24924.

Carmeliet., P. (2003). Angiogenesis in health and disease. Nat Med., 9(6), 653-660.

Chang, H.S., Lin, C.H., Yang, C.H., Liang, Y.J., Yu, W.C.(2010). The human papillomavirus-16 (HPV-16) oncoprotein E7 conjugates with and mediates the role of the transforming growth factor-beta inducible early gene 1 (TIEG1) in apoptosis. Int J Biochem Cell Biol. 42(11):1831-9

Chulada, P., Thompson, M., Mahler, J., Doyle, C., Gaul, B., Lee, C., et al. (2000 ). Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res., 60(17), 4705-4708.

Cipollone, F., Fazia, M., Mincione, G., Iezzi, A., Pini, B., Cuccurullo, C., et al. (2004). Increased expression of transforming growth factor-beta1 as a stabilizing factor in human atherosclerotic plaques. Stroke, 35(10), 2253-2257.

Daikoku, T., Wang, D., Tranguch, S., Morrow, J. D., Orsulic, S., DuBois, R. N., et al. (2005). Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian epithelial cancer. [Research Support, N.I.H., Extramural. Cancer Res, 65(9), 3735-3744.

Diaz, A., Chepenik, K., Korn, J., Reginato, A., & Jimenez, S. (1998). Differential regulation of cyclooxygenases 1 and 2 by interleukin-1 beta, tumor necrosis factor-alpha, and transforming growth factor-beta 1 in human lung fibroblasts. Exp Cell Res. , 241(1)(1), 222-229.

Dickson, M., Martin, J., Cousins, F., Kulkarni, A., Karlsson, S., & ., R. A. (1995 ). Defective haematopoiesis and vasculogenesis in transforming growth factor-
b1 knock out mice. Development. , 121(6), 1845-1854.

Ding, X., Hennig, R., & Adrian, T. (2003). Lipoxygenase and cyclooxygenase metabolism new insights in treatment and chemoprevention of pancreatic cancer. Mol Cancer., 2(10), 1-12.

Egan, K. M., Wang, M., Fries, S., Lucitt, M. B., Zukas, A. M., Pure, E., et al. (2005). Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism. Comparative Study. Circulation, 111(3), 334-342.

Ellenrieder, V. (2008). TGFbeta regulated gene expression by Smads and Sp1KLF-like transcription factors in cancer. Anticancer Res., 28(3A), 1531-1539.

Erovic, B. M., Woegerbauer, M., Pammer, J., Selzer, E., Grasl, M., & Thurnher, D. (2008). Strong evidence for up-regulation of cyclooxygenase-1 in head and neck cancer. [Comparative Study]. Eur J Clin Invest, 38(1), 61-66.

Funk, C., Funk, L., Kennedy, M., Pong, A., & Fitzgerald, G. (1991). Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J. , 5(6), 2304-2312.

Ghosh, J., Murphy, M. O., Turner, N., Khwaja, N., Halka, A., Kielty, C. M., et al. (2005). The role of transforming growth factor beta1 in the vascular system. [Review]. Cardiovasc Pathol, 14(1), 28-36.

Gibson, L. L., Hahner, L., Osborne-Lawrence, S., German, Z., Wu, K. K., Chambliss, K. L., et al. (2005). Molecular basis of estrogen-induced cyclooxygenase type 1 upregulation in endothelial cells. Circ Res, 96(5), 518-525.

Goumans, M.-J., Lebrin, F., & Valdimarsdottir, G. (2003). Controlling the Angiogenic SwitchA Balance between Two Distinct TGF-b Receptor Signaling Pathways. Trends Cardiovasc Med, 13(7), 301-307.

Goumans, M., Valdimarsdottir, G., Itoh, S., Rosendahl, A., Sideras, P., & Dijke, P. t. (2002). Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J. , 21(7), 1743-1753.

Guillaumond, F., Grechez-Cassiau, A., Subramaniam, M., Brangolo, S., Peteri-Brunback, B., Staels, B., et al. (2010). Kruppel-like factor KLF10 is a link between the circadian clock and metabolism in liver. Mol Cell Biol, 30(12), 3059-3070.

Gupta, R., Tejada, L., Tong, B., Das, S., Morrow, J., Dey, S., et al. (2003). Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer. Cancer Res. , 63(5), 906-911.

Hanahan, D., & Folkman, J. (1996). Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis. Cell., 86(3), 353-364.

Hawse, J. R., Cicek, M., Grygo, S. B., Bruinsma, E. S., Rajamannan, N. M., van Wijnen, A. J., et al. (2011). TIEG1/KLF10 modulates Runx2 expression and activity in osteoblasts.. PLoS One, 6(4), e19429.

Houchen, C., Stenson, W., & Cohn, S. (2000). Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury. Am J Physiol Gastrointest Liver Physiol. , 279(5), G858-865.

Holden, N. S. and Tacon, C.E. (2011) Principles and problems of the electrophoretic mobility shift assay. J of Pharmacological and Toxicological Methods.,63(1),7-14

Hsu, C. F., Sui, C. L., Wu, W. C., Wang, J. J., Yang, D. H., Chen, Y. C., et al. (2011). Klf10 induces cell apoptosis through modulation of BI-1 expression and Ca2+ homeostasis in estrogen-responding adenocarcinoma cells. Int J Biochem Cell Biol, 43(4), 666-673.

Imataka, H., Sogawa, K., Yasumoto, K., Kikuchi, Y., Sasano, K., Kobayashi, A., et al. (1992). Two regulatory proteins that bind to the basic transcription element (BTE), a GC box sequence in the promoter region of the rat P-4501A1 gene. EMBO J. , 11(10)), 3663-3671.

Jackson, B., Goldstein, R., Roy, R., Cozzani, M., Taylor, L., & Polgar, P. (1993). Effects of transforming growth factor beta and interleukin-1 beta on expression of cyclooxygenase 1 and 2 and phospholipase A2 mRNA in lung fibroblasts and endothelial cells in culture. Biochem Biophys Res Commun. , 197(3), 1465-1474.

Johnsen, S. A., Subramaniam, M., Effenberger, K. E., & Spelsberg, T. C. (2004). The TGF? inducible early gene plays a central role in the anti-proliferative response to TGF? Signal Transduction, 4(1-2), 29-35.

Jun, S., Chen, Z., Pace, M., & Shaul, P. (1998 ). Estrogen upregulates cyclooxygenase-1 gene expression in ovine fetal pulmonary artery endothelium. J Clin Invest. , 102(1), 176-183.

Kaczynski, J., Zhang, J. S., Ellenrieder, V., Conley, A., Duenes, T., Kester, H., et al. (2001). The Sp1-like protein BTEB3 inhibits transcription via the basic transcription element box by interacting with mSin3A and HDAC-1 co-repressors and competing with Sp1. J Biol Chem, 276(39), 36749-36756.

Kaplan, M., Olschowka, J., & O'Banion, M. (1997 ). Cyclooxygenase-1 behaves as a delayed response gene in PC12 cells differentiated by nerve growth factor. J Biol Chem., 272(30), 18534-18537.

Kim, J., Shin, S., Subramaniam, M., Bruinsma, E., Kim, T., Hawse, J., et al. (2010). Histone demethylase JARID1BKDM5B is a corepressor of TIEG1/KLF10. Biochem Biophys Res Commun, 401(3), 412-416.

Kim, J., Wang, J., Bambra, C., Das, S., Dey, S., & Fazleabas, A. (1999). Expression of cyclooxygenase-1 and -2 in the baboon endometrium during the menstrual cycle and pregnancy. Endocrinology, 140(6), 2672-2678.

Koochekpour, S., Merzak, A., & Pilkington, G. (1996). Vascular endothelial growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells in vitro. Cancer Lett. , 102(1-2), 209-215.

Koutouzis, M., Nomikos, A., Nikolidakis, S., Tzavara, V., Andrikopoulos, V., Nikolaou, N., et al. (2007). Statin treated patients have reduced intraplaque angiogenesis in carotid endarterectomy specimens. Atherosclerosis, 192(2), 457-463.

Kraemer, S., Meade, E., & DeWitt, D. (1992). Prostaglandin endoperoxide synthase gene structure: identification of the transcriptional start site and 5'-flanking regulatory sequences. Arch Biochem Biophys., 293(2), 391-400.

Langenbach, R., Morham, S., Tiano, H., Loftin, C., Ghanayem, B., Chulada, P., et al. (1995). Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell. , 83(3), 483-492.

Larsson, J., Goumans, M., Sjöstrand, L., Rooijen, M. v., Ward, D., Levéen, P., et al. (2001 ). Abnormal angiogenesis but intact hematopoietic potential in TGF-β type I receptor-deficient mice. EMBO J., 20(7), 1663-1673.

Lebrin, F., Deckers, M., Bertolino, P., & Ten Dijke, P. (2005). TGF-beta receptor function in the endothelium. Cardiovasc Res, 65(3), 599-608.

Lin, C.-Y. (2010). Study the correlation between Klf10 deficiency mice and type-2 diabetes mellitus. National Cheng Kung University.

Liotta, L., Steeg, P., & Stetler-Stevenson, W. (1991). Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell., 64(2), 327-336.

Loftin, C., Tiano, H., & Langenbach, R. (2002 ). Phenotypes of the COX-deficient mice indicate physiological and pathophysiological roles for COX-1 and COX-2. Prostaglandins Other Lipid Mediat. , 68(69), 177-185.

Losordo, D. W., & Isner, J. M. (2001). Estrogen and Angiogenesis : A Review. Arteriosclerosis, Thrombosis, and Vascular Biology, 21(1), 6-12.

McClelland, S., Gawaz, M., Kennerknecht, E., Konrad, C. S., Sauer, S., Schuerzinger, K., et al. (2009). Contribution of cyclooxygenase-1 to thromboxane formation, platelet-vessel wall interactions and atherosclerosis in the ApoE null mouse. Atherosclerosis, 202(1), 84-91.

McConnell, B. B., & Yang, V. W. (2010). Mammalian Kruppel-like factors in health and diseases. Physiol Rev, 90(4), 1337-1381.

Morales, D., McGowan, K., Grant, D., Maheshwari, S., Bhartiya, D., Cid, M., et al. (1995). Estrogen Promotes Angiogenic Activity in Human Umbilical Vein Endothelial Cells In Vitro and in a Murine Model Circulation. , 91, 755-763.

Morita, I. (2002). Distinct functions of COX-1 and COX-2. Prostaglandins Other Lipid Mediat., 68(69), 165-175.

Nagai, R. z., Friedman, S. L., & Kasuga, M. (2009). The biology of Krüppel-like factors. Tokyo: Springer.

Nakagawa, T., Li, J., Garcia, G., Mu, W., Piek, E., Böttinger, E., et al. (2004 ). TGF-beta induces proangiogenic and antiangiogenic factors via parallel but distinct Smad pathways. Kidney Int., 66(2), 605-613.

Niho, N., Kitamura, T., Takahashi, M., Mutoh, M., Sato, H., Matsuura, M., et al. (2006). Suppression of azoxymethane-induced colon cancer development in rats by a cyclooxygenase-1 selective inhibitor, mofezolac. Cancer Sci, 97(10), 1011-1014.

Nikol, S., Isner, J., Pickering, J., Kearney, M., Leclerc, G., & Weir, L. (1992). Expression of transforming growth factor-beta 1 is increased in human vascular restenosis lesions. J Clin Invest. , 90(4), 1582-1592.

Noti, J. D., Johnson, A. K., & Dillon, J. D. (2004). The zinc finger transcription factor transforming growth factor beta-inducible early gene-1 confers myeloid-specific activation of the leukocyte integrin CD11d promoter. J Biol Chem, 279(26), 26948-26958.

Ospina, J. A. (2002). 17beta-Estradiol Increases Rat Cerebrovascular Prostacyclin Synthesis by Elevating Cyclooxygenase-1 and Prostacyclin Synthase. Stroke, 33(2), 600-605.

Pai, R., Szabo, I. L., Soreghan, B. A., Atay, S., Kawanaka, H., & Tarnawski, A. S. (2001). PGE(2) stimulates VEGF expression in endothelial cells via ERK2/JNK1 signaling pathways. Biochem Biophys Res Commun, 286(5), 923-928.

Paigen, B., Kovats, S., Chapman, M., & Lin, C. (1987 ). Characterization of a genetic difference in the platelet aggregation response of two inbred mouse strains, C57BL/6 and C3H/He. Atherosclerosis, 64(2-3), 181-190.

Pardali, E., Goumans, M. J., & ten Dijke, P. (2010). Signaling by members of the TGF-beta family in vascular morphogenesis and disease. Trends Cell Biol, 20(9), 556-567.

Pardali, E., & Ten Dijke, P. (2012). TGFbeta signaling and cardiovascular diseases. Int J Biol Sci, 8(2), 195-213.

Pepper, M. (1997). Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev., 8(1), 21-43.

Pratico, D., Tillmann, C., Zhang, Z. B., Li, H., & FitzGerald, G. A. (2001). Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice. Proc Natl Acad Sci U S A, 98(6), 3358-3363.

Schulick, A., Taylor, A., Zuo, W., Qiu, C., Dong, G., Woodward, R., et al. (1998). Overexpression of transforming growth factor beta1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia. Proc Natl Acad Sci U S A. , 95(12), 6983-6988.

Schuster., N., & Krieglstein., K. (2002). Mechanisms of TGF-beta-mediated apoptosis.. Cell Tissue Res, 307(1), 1-14.

Secchiero, P., Gonelli, A., Ciabattoni, G., Melloni, E., Grill, V., Rocca, B., et al. (2002). TNF-related apoptosis-inducing ligand (TRAIL) up-regulates cyclooxygenase (COX)-1 activity and PGE(2) production in cells of the myeloid lineage. J Leukoc Biol., 72(5), 986-994.

Soares, R., Guo, S., Gärtner, F., Schmitt, F., & Russo, J. (2003). 17 beta -estradiol-mediated vessel assembly and stabilization in tumor angiogenesis requires TGF beta and EGFR crosstalk. Angiogenesis., 6(4), 271-281.

Sogawa, K., Kikuchi, Y., Imataka, H., & Fujii-Kuriyama, Y. (1993). Comparison of DNA-binding properties between BTEB and Sp1. J Biochem. , 114(4), 605-609.

Subramaniam, M., Hawse, J. R., Rajamannan, N. M., Ingle, J. N., & Spelsberg, T. C. (2010). Functional role of KLF10 in multiple disease processes. [Research Support, N.I.H., Extramural. Biofactors, 36(1), 8-18.

Sun, L., Reding, T., Bain, M., Heikenwalder, M., Bimmler, D., & Graf, R. (2007). Prostaglandin E2 modulates TNF-alpha-induced MCP-1 synthesis in pancreatic acinar cells in a PKA-dependent manner. Am J Physiol Gastrointest Liver Physiol., 293(6), G1196-1204.

Tachibana, I., Imoto, M., Adjei, P., Gores, G., Subramaniam, M., Spelsberg, T., et al. (1997 ). Overexpression of the TGFbeta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells. J Clin Invest. , 99(10), 2365-2374.

Tailor, A., Wood, K., Wallace, J., Specian, R., & Granger, D. (2007). Roles of platelet and endothelial cell COX-1 in hypercholesterolemia-induced microvascular dysfunction. Am J Physiol Heart Circ Physiol, 293(6), 3636-3642.

Tsujii, M., Kawano, S., Tsuji, S., Sawaoka, H., Hori, M., & DuBois, R. (1998). Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell., 93(5), 705-716.

Turner, J., & Crossley, M. (1998). Cloning and characterization of mCtBP2, a co-repressor that. EMBO J., 17(17), 5129-5140.

Ulrich, C. M., Bigler, J., & Potter, J. D. (2006). Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. [Review]. Nat Rev Cancer, 6(2), 130-140.

Unsicker, K., & ., K. K. (2000). Co-activation of TGF-ss and cytokine signaling pathways are required for neurotrophic functions. Cytokine Growth Factor Rev. , 11(1-2), 97-102.

Virdis, A., Ghiadoni, L., & Taddei, S. (2010). Human endothelial dysfunction: EDCFs. [Review]. Pflugers Arch, 459(6), 1015-1023.

Wara, A. K., Foo, S., Croce, K., Sun, X., Icli, B., Tesmenitsky, Y., et al. (2011). TGF-beta1 signaling and Kruppel-like factor 10 regulate bone marrow-derived proangiogenic cell differentiation, function, and neovascularization. Blood, 118(24), 6450-6460.

Wen, F., Sköld, C., Liu, X., Ertl, R., Zhu, Y., Kohyama, T., et al. (2001). Glucocorticoids and TGF-beta1 synergize in augmenting fibroblast mediated contraction of collagen gels. Inflammation, 25(2), 109-117.

Willems-Widyastuti, A., Alagappan, V., Arulmani, U., Vanaudenaerde, B., de Boer, W., Mooi, W., et al. (2011). Transforming growth factor-beta 1 induces angiogenesis in vitro via VEGF production in human airway smooth muscle cells. Indian J Biochem Biophys, 48(4), 262-269.

Wu, W.-C. (2010). Effect of KLF10 modulating pathway, altering the BI-1(Bax inhibitor-1) expression, in high-dose estrogen induced apoptosis. National Cheng Kung University.

Xu, X., Tang, J., Chen, X., Wang, L., & Wu, K. (1997). Involvement of two Sp1 elements in basal endothelial prostaglandin H synthase-1 promoter activity. J Biol Chem, 222(11), 6943-6950.

Zhang, J. S., Moncrieffe, M. C., Kaczynski, J., Ellenrieder, V., Prendergast, F. G., & Urrutia, R. (2001). A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A. Mol Cell Biol, 21(15), 5041-5049.

校內：2014-07-06公開
校外：2015-07-06公開

簡易檢索 / 詳目顯示

相關論文