第二型內皮素與第一型類胰島素生長因子對3T3-L1前脂肪細胞生長刺激作用的信息傳導路徑

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鄒宇涵(Yu-Han Tsou) 查詢紙本館藏

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論文名稱

第二型內皮素與第一型類胰島素生長因子對3T3-L1前脂肪細胞生長刺激作用的信息傳導路徑
(Signal transduction pathway of endothelin-2 with IGF-I in the growth stimulation of 3T3-L1 preadipocytes)

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至系統瀏覽論文 (2025-11-25以後開放)

摘要(中)

內皮素（ETs）是一種21個氨基酸的肽激素，從豬主動脈內皮細胞培養上清液中分離出來，被稱為有效的血管收縮劑和加壓劑。儘管有文獻指出ETs增強第一型類胰島素生長因子（IGF-I）對前列腺癌細胞生長的刺激作用，但尚未發現ET-2是否與IGF-I有相互作用在脂肪細胞的報導。使用3T3-L1前脂肪細胞，我們發現單獨的ET-2對細胞生長沒有影響，如在細胞數量，細胞存活和BrdU incorporation的變化所表明。在存在IGF-1的情況下，ET-2增強了IGF-1誘導的細胞數量和細胞增殖的增加。當檢驗ET-2信號通路時，透過內皮素受體的特異性抑製劑ETAR拮抗劑（BQ610）而不是ETBR拮抗劑（BQ788）的預處理阻止了ET-2對IGF-I誘導的細胞數量和細胞存活增加的增強作用。進一步的在Western blot中表明，ET-2、IGF-I及其組合傾向於時間依賴性的刺激AKT、ERK和STAT3蛋白的磷酸化。有趣的是，與單獨的IGF-I相比，ET-2在一小時增強了IGF-I刺激的STAT3磷酸化蛋白，但未增強AKT或ERK1/2。但是，在15和30分鐘時預處理ET-2可以增強IGF-I刺激的AKT和ERK蛋白的磷酸化。此外，預處理STAT3抑制劑（AG490）、ERK1/2抑制劑（U0126）和PI3K/AKT抑制劑（Wortmannin）阻止了ET-2和IGF-I對細胞數和細胞存活的刺激，同時也分別降低各自pSTAT3，pAKT和pERK蛋白水平。總之，STAT3以及較小程度的AKT和ERK蛋白對於ET-2和IGF-I以ETAR依賴性而不是ETBR依賴性的方式對前脂肪細胞的生長產生協同作用是必需的。

摘要(英)

Endothelins (ETs) are a 21 amino acid (aa) peptide hormone that was known as a potent vasoconstrictor and pressor substance isolated from the culture supernatant of porcine aortic endothelial cells. Although the ETs have been also reported to potentiate the stimulatory effect of insulin-like growth factor (IGF)-I on the growth of prostate cancer cells, no reports are found whether ET-2 interacts with IGF-I in fat cells. Using 3T3-L1 preadipocytes, we found that ET-2 alone had no effect on cell growth, as indicated by changes in levels of cell number, BrdU incorporation, and cell viability. In the presence of IGF-I, ET-2 enhanced IGF-I-induced increases in both cell number and cell proliferation. When the ET-2 signaling pathway was examined, pretreatment with the specific inhibitors of endothelin receptors, ETAR antagonist (BQ610) but not ETBR antagonist (BQ788), prevented the enhancing effect of ET-2 on IGF-I-induced increases in both cell number and cell viability. Further Western blotting analysis showed that ET-2, IGF-I, and their combination tended to time-dependently stimulate phosphorylations of AKT, ERK, and STAT3 proteins. Interestingly, ET-2 at 1 h enhanced IGF-I-stimulated phosphorylation of STAT3, but not AKT or ERK1/2, proteins when compared to IGF-I alone. But, pretreatment with ET-2 at 15 and 30 min enhanced IGF-I-stimulated phosphorylation of AKT and ERK proteins. Moreover, pre-treatment with STAT3 inhibitor (AG490), ERK1/2 inhibitor (U0126), and PI3K/AKT inhibitor (wortmannin) prevented the stimulation of ET-2 and IGF-I in cell number and cell viability, respectively, as well as reducing the level of respective pSTAT3, pAKT, and pERK proteins. In conclusions, STAT3 and, to a lesser extent of AKT and ERK proteins are necessary for the synergistic effect of ET-2 and IGF-I on the growth of preadipocytes in an ETAR-dependent and ETBR-independent manner.

關鍵字(中)

★ 第二型內皮素
★ 第一型類胰島素生長因子
★ 前脂肪細胞

關鍵字(英)

★ endothelin-2
★ IGF-I
★ preadipocyte

論文目次

摘要 I
ABSTRACT II
致謝 III
目錄 IV
表目錄 VII
圖目錄 VIII
縮寫與全名對照表 IX
壹、前言 1
1-1 肥胖症與脂肪細胞 1
1-2 內皮素 2
1-2-1 第一型和第三型內皮素的差異 2
1-2-2第二型內皮素 3
1-2-3 Endothelin之訊息傳導路徑 3
1-2-4 ET-2與脂肪細胞的關係及其訊息傳導 4
1-3 第一型類胰島素生長因子 5
1-3-1 IGF-I之特性 5
1-3-2 IGF-I之訊息傳導路徑 5
1-3-3 IGF-I與脂肪細胞之關係及訊息傳導 6
1-4 研究動機與目的 6
貳、材料與方法 7
2-1 實驗材料 7
2-2 實驗方法 7
2-2-1 細胞培養 7
2-2-2 ET-2、IGF-I和抑制劑處理 7
2-2-3 細胞生長實驗 7
2-2-3-1 細胞計數 7
2-2-3-2 細胞存活率試驗（MTT assay） 8
2-2-3-3 細胞增殖分析（BrdU incorporation） 8
2-2-4 蛋白質萃取與定量 9
2-2-5 西方墨點法 9
2-3 統計分析 11
參、結果 12
3-1 ET-2和IGF-I對3T3-L1生長的影響 12
3-2 ET-2對IGF-I 之強化作用是透過ETAR不是ETBR而影響細胞的生長 12
3-3 ET-2對IGF-I之強化作用是透過 STAT3蛋白而影響3T3-L1細胞生長 13
3-4 ET-2和IGF-I可能透過PI3K/AKT蛋白而影響細胞生長 14
3-5 ET-2和IGF-I可能透過MAPK家族蛋白影響細胞生長 15
3-6 STAT3，AKT和EKR1/2蛋白之間的交互作用（CROSS TALK） 16
肆、討論 18
伍、結論 22
陸、參考文獻 23
表1、材料名稱、產品型號及採購來源 34
表 2、抗體來源與稀釋比例 36
圖一、ET-2和IGF-I的協同作用增加了3T3-L1前脂肪細胞中的（A）細胞數、（B）細胞增殖和（C）細胞增殖存活率。 37
圖二、ET-2和IGF-I的協同作用是通過ETAR路徑增加前脂肪細胞的生長，但不通過ETBR。 40
圖三、JAK2/STAT3抑製劑（AG490）抑制ET-2對IGF-I刺激3T3-L1生長之強化作用 42
圖四、PI3K/AKT抑製劑（Wortmannin）抑制ET-2對IGF-I刺激前脂肪細胞生長之強化作用。 44
圖五、ERK1/2抑製劑（U0126）抑制ET-2和IGF-I刺激前脂肪細胞生長之協同作用。 46
圖六、透過STAT3拮抗劑（AG490）、PI3K/AKT拮抗劑（Wortmannin）以及ERK1/2拮抗劑（U0126）觀察各蛋白之間的交互作用。 48
圖七、內皮素-2對3T3-L1前脂肪細胞生長之機制。 49
圖八、IGF-I對3T3-L1前脂肪細胞生長之機制。 50
圖九、ET-2和IGF-I之協同作用對3T3-L1前脂肪細胞生長之機制。 51
柒、附錄 52
附錄一、ET-2, IGF-I和抑制劑配製方法與濃度 52
附錄二、Lysis buffer preparation (1mL) 53
附錄三、使用試劑之配方 54
附錄四、JNK，cJun，p38之time course。 57
附錄五、不同血清條件下對ET-2和IGF-I之協同作用之影響 58
附錄六、無血清條件下，處理藥物1小時之蛋白質的表現。 59
附錄七、實驗中每種抗體的完整印跡圖。 61

參考文獻

1. Aggarwal, B. B., Kunnumakkara, A. B., Harikumar, K. B., Gupta, S. R., Tharakan, S. T., Koca, C., Dey, S., & Sung, B. (2009). Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship?. Annals of the New York Academy of Sciences, 1171, 59–76. https://doi.org/10.1111/j.1749-6632.2009.04911.x
2. Barton, M., & Yanagisawa, M. (2008). Endothelin: 20 years from discovery to therapy. Canadian journal of physiology and pharmacology, 86(8), 485–498. https://doi.org/10.1139/Y08-059Canadian Journal of Physiology and Pharmacology, 86(8), 485–498. https://doi.org/10.1139/y08-059
3. Binz, N., Rakoczy, E. P., Ali Rahman, I. S., Vagaja, N. N., & Lai, C. M. (2016). Biomarkers for Diabetic Retinopathy - Could Endothelin 2 Be Part of the Answer?. PloS one, 11(8), e0160442. https://doi.org/10.1371/journal.pone.0160442
4. Boney, C. M., Sekimoto, H., Gruppuso, P. A., & Frackelton, A. R., Jr (2001). Src family tyrosine kinases participate in insulin-like growth factor I mitogenic signaling in 3T3-L1 cells. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 12(7), 379–386.
5. Boney, C. M., Smith, R. M., & Gruppuso, P. A. (1998). Modulation of insulin-like growth factor I mitogenic signaling in 3T3-L1 preadipocyte differentiation. Endocrinology, 139(4), 1638–1644. https://doi.org/10.1210/endo.139.4.5920
6. Booz, G. W., Day, J. N., & Baker, K. M. (2003). Angiotensin II effects on STAT3 phosphorylation in cardiomyocytes: evidence for Erk-dependent Tyr705 dephosphorylation. Basic research in cardiology, 98(1), 33–38. https://doi.org/10.1007/s00395-003-0387-x
7. Bossy-Wetzel, E., Bakiri, L., & Yaniv, M. (1997). Induction of apoptosis by the transcription factor c-Jun. The EMBO journal, 16(7), 1695–1709. https://doi.org/10.1093/emboj/16.7.1695
8. Caro, J. F., Dohm, L. G., Pories, W. J., & Sinha, M. K. (1989). Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes/metabolism reviews, 5(8), 665–689. https://doi.org/10.1002/dmr.5610050804
9. Chang, H. H., Huang, Y. M., Wu, C. P., Tang, Y. C., Liu, C. W., Huang, C. H., Ho, L. T., Wu, L. Y., Kuo, Y. C., & Kao, Y. H. (2012). Endothelin-1 stimulates suppressor of cytokine signaling-3 gene expression in adipocytes. General and comparative endocrinology, 178(3), 450–458. https://doi.org/10.1016/j.ygcen.2012.06.024
10. Chang, I., Bramall, A. N., Baynash, A. G., Rattner, A., Rakheja, D., Post, M., Joza, S., McKerlie, C., Stewart, D. J., McInnes, R. R., & Yanagisawa, M. (2013). Endothelin-2 deficiency causes growth retardation, hypothermia, and emphysema in mice. The Journal of clinical investigation, 123(6), 2643–2653. https://doi.org/10.1172/JCI66735
11. Kim, J. H., Park, S. H., Nam, S. W., Kwon, H. J., Kim, B. W., Kim, W. J., & Choi, Y. H. (2011). Curcumin stimulates proliferation, stemness acting signals and migration of 3T3-L1 preadipocytes. International journal of molecular medicine, 28(3), 429–435. https://doi.org/10.3892/ijmm.2011.680
12. Chung, J., Uchida, E., Grammer, T. C., & Blenis, J. (1997). STAT3 serine phosphorylation by ERK-dependent and -independent pathways negatively modulates its tyrosine phosphorylation. Molecular and cellular biology, 17(11), 6508–6516. https://doi.org/10.1128/mcb.17.11.6508
13. Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E. (1997). Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 91(2), 231–241. https://doi.org/10.1016/s0092-8674(00)80405-5
14. Davenport, A. P., Hyndman, K. A., Dhaun, N., Southan, C., Kohan, D. E., Pollock, J. S., Pollock, D. M., Webb, D. J., & Maguire, J. J. (2016). Endothelin. Pharmacological reviews, 68(2), 357–418. https://doi.org/10.1124/pr.115.011833
15. Deng, J., Hua, K., Lesser, S. S., & Harp, J. B. (2000). Activation of signal transducer and activator of transcription-3 during proliferative phases of 3T3-L1 adipogenesis. Endocrinology, 141(7), 2370–2376. https://doi.org/10.1210/endo.141.7.7551
16. Duncan, S. A., Zhong, Z., Wen, Z., & Darnell, J. E., Jr (1997). STAT signaling is active during early mammalian development. Developmental dynamics : an official publication of the American Association of Anatomists, 208(2), 190–198. https://doi.org/10.1002/(SICI)1097-0177(199702)208:2<190::AID-AJA6>3.0.CO;2-D
17. Emoto, N., & Yanagisawa, M. (1995). Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum. The Journal of biological chemistry, 270(25), 15262–15268. https://doi.org/10.1074/jbc.270.25.15262
18. Gardiner, S. M., Kemp, P. A., & Bennett, T. (1992). Inhibition by phosphoramidon of the regional haemodynamic effects of proendothelin-2 and -3 in conscious rats. British journal of pharmacology, 107(2), 584–590. https://doi.org/10.1111/j.1476-5381.1992.tb12787.x
19. Ghoul, A., Serova, M., Le Tourneau, C., Aïssat, N., Hammel, P., Raymond, E., & Faivre, S. (2007). Role of the endothelins and endothelin receptors in cancer cell signaling and angiogenesis. Targeted Oncology, 2(3), 181-191. doi:10.1007/s11523-007-0056-3
20. Green, H., & Meuth, M. (1974). An established pre-adipose cell line and its differentiation in culture. Cell, 3(2), 127–133. https://doi.org/10.1016/0092-8674(74)90116-0
21. Grimshaw, M. J., Hagemann, T., Ayhan, A., Gillett, C. E., Binder, C., & Balkwill, F. R. (2004). A role for endothelin-2 and its receptors in breast tumor cell invasion. Cancer research, 64(7), 2461–2468. https://doi.org/10.1158/0008-5472.can-03-1069
22. Hakuno, F., & Takahashi, S.-I. (2018). 40 YEARS OF IGF1: IGF1 receptor signaling pathways. Journal of Molecular Endocrinology, 61(1), T69–T86. https://doi.org/10.1530/jme-17-0311
23. Heim M. H. (1999). The Jak-STAT pathway: cytokine signalling from the receptor to the nucleus. Journal of receptor and signal transduction research, 19(1-4), 75–120. https://doi.org/10.3109/10799899909036638
24. Hohos, N. M., Elliott, E. M., Giornazi, A., Silva, E., Rice, J. D., & Skaznik-Wikiel, M. E. (2021). High-Fat Diet Induces an Ovulatory Defect Associated with Dysregulated Endothelin-2 in Mice. Reproduction (Cambridge, England), REP-20-0290.R2. Advance online publication. https://doi.org/10.1530/REP-20-0290
25. Kim, A. R., Yoon, B. K., Park, H., Seok, J. W., Choi, H., Yu, J. H., Choi, Y., Song, S. J., Kim, A., & Kim, J. W. (2016). Caffeine inhibits adipogenesis through modulation of mitotic clonal expansion and the AKT/GSK3 pathway in 3T3-L1 adipocytes. BMB reports, 49(2), 111–115. https://doi.org/10.5483/bmbrep.2016.49.2.128
26. Ku, H. C., Liu, H. S., Hung, P. F., Chen, C. L., Liu, H. C., Chang, H. H., Tsuei, Y. W., Shih, L. J., Lin, C. L., Lin, C. M., & Kao, Y. H. (2012). Green tea (-)-epigallocatechin gallate inhibits IGF-I and IGF-II stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway. Molecular nutrition & food research, 56(4), 580–592. https://doi.org/10.1002/mnfr.201100438
27. Laviola, L., Natalicchio, A., & Giorgino, F. (2007). The IGF-I signaling pathway. Current pharmaceutical design, 13(7), 663–669. https://doi.org/10.2174/138161207780249146
28. Le Roith, D., Bondy, C., Yakar, S., Liu, J. L., & Butler, A. (2001). The somatomedin hypothesis: 2001. Endocrine reviews, 22(1), 53–74. https://doi.org/10.1210/edrv.22.1.0419
29. Lee, D. S., Choi, H., Han, B. S., Kim, W. K., Lee, S. C., Oh, K. J., & Bae, K. H. (2016). c-Jun regulates adipocyte differentiation via the KLF15-mediated mode. Biochemical and biophysical research communications, 469(3), 552–558. https://doi.org/10.1016/j.bbrc.2015.12.035
30. Lee, J. G., Zheng, R., McCafferty-Cepero, J. M., Burnstein, K. L., Nanus, D. M., & Shen, R. (2009). Endothelin-1 enhances the expression of the androgen receptor via activation of the c-myc pathway in prostate cancer cells. Molecular carcinogenesis, 48(2), 141–149. https://doi.org/10.1002/mc.20462
31. LeRoith, D. (1991). Insulin-like Growth Factors: Molecular and Cellular Aspects. In Google Books. CRC Press.
32. LeRoith, D., Werner, H., Beitner-Johnson, D., & Roberts, C. T., Jr (1995). Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocrine reviews, 16(2), 143–163. https://doi.org/10.1210/edrv-16-2-143
33. Levy, D. E., & Lee, C. K. (2002). What does Stat3 do?. The Journal of clinical investigation, 109(9), 1143–1148. https://doi.org/10.1172/JCI15650
34. Lewitt, M. S., Dent, M. S., & Hall, K. (2014). The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus. Journal of clinical medicine, 3(4), 1561–1574. https://doi.org/10.3390/jcm3041561
35. Liefeldt, L., Rylski, B., Walcher, F., Manhart, J., Kron, S., Rosenke, Y. W., Paul, M., Neumayer, H. H., Amann, K., & Peters, H. (2010). Effects of transgenic endothelin-2 overexpression on diabetic cardiomyopathy in rats. European journal of clinical investigation, 40(3), 203–210. https://doi.org/10.1111/j.1365-2362.2009.02251.x
36. Ling, L., Maguire, J. J., & Davenport, A. P. (2013). Endothelin-2, the forgotten isoform: emerging role in the cardiovascular system, ovarian development, immunology and cancer. British journal of pharmacology, 168(2), 283–295. https://doi.org/10.1111/j.1476-5381.2011.01786.x
37. Lopez-Bergami, P., Huang, C., Goydos, J. S., Yip, D., Bar-Eli, M., Herlyn, M., Smalley, K. S., Mahale, A., Eroshkin, A., Aaronson, S., & Ronai, Z. (2007). Rewired ERK-JNK signaling pathways in melanoma. Cancer cell, 11(5), 447–460. https://doi.org/10.1016/j.ccr.2007.03.009
38. Machinal-Quélin, F., Dieudonné, M. N., Leneveu, M. C., Pecquery, R., & Giudicelli, Y. (2002). Proadipogenic effect of leptin on rat preadipocytes in vitro: activation of MAPK and STAT3 signaling pathways. American journal of physiology. Cell physiology, 282(4), C853–C863. https://doi.org/10.1152/ajpcell.00331.2001
39. Marrero, M. B., Schieffer, B., Li, B., Sun, J., Harp, J. B., & Ling, B. N. (1997). Role of Janus kinase/signal transducer and activator of transcription and mitogen-activated protein kinase cascades in angiotensin II- and platelet-derived growth factor-induced vascular smooth muscle cell proliferation. The Journal of Biological Chemistry, 272(39), 24684–24690. https://doi.org/10.1074/jbc.272.39.24684
40. Megeney, L. A., Perry, R. L., LeCouter, J. E., & Rudnicki, M. A. (1996). bFGF and LIF signaling activates STAT3 in proliferating myoblasts. Developmental genetics, 19(2), 139–145. https://doi.org/10.1002/(SICI)1520-6408(1996)19:2<139::AID-DVG5>3.0.CO;2-A
41. Miki, T., Hilal-Dandan, R., Brunton, L. L., Sévigny, J., Lai, K.-O., Ip, N. Y., Zhou, R., Milanesi, F., Volkmann, N., Scita, G., Hanein, D., Pouysségur, J., Lenormand, P., Klinger, S., Meloche, S., Dahlman-Wright, K., & Zhao, C. (2012). Endothelin A Receptor (ETAR). Encyclopedia of Signaling Molecules, 545–551. https://doi.org/10.1007/978-1-4419-0461-4_616
42. Miyauchi, T., & Sakai, S. (2019). Endothelin and the heart in health and diseases. Peptides, 111, 77–88. https://doi.org/10.1016/j.peptides.2018.10.002
43. Monno, S., Newman, M. V., Cook, M., & Lowe, W. L. (2000). Insulin-Like Growth Factor I Activates c-Jun N-Terminal Kinase in MCF-7 Breast Cancer Cells1. Endocrinology, 141(2), 544–550. https://doi.org/10.1210/endo.141.2.7307
44. Naihan, X., Yuanzhi, L., Yaou, Z., & David A., G. (2012). Akt: A Double-Edged Sword in Cell Proliferation and Genome Stability. Journal of Oncology, 2012, 1–15. https://doi.org/10.1155/2012/951724
45. Palanisamy, G. S., Cheon, Y.-P., Kim, J., Kannan, A., Li, Q., Sato, M., Mantena, S. R., Sitruk-Ware, R. L., Bagchi, M. K., & Bagchi, I. C. (2006). A Novel Pathway Involving Progesterone Receptor, Endothelin-2, and Endothelin Receptor B Controls Ovulation in Mice. Molecular Endocrinology, 20(11), 2784–2795. https://doi.org/10.1210/me.2006-0093
46. Puche, J. E., & Castilla-Cortázar, I. (2012). Human conditions of insulin-like growth factor-I (IGF-I) deficiency. Journal of Translational Medicine, 10(1), 224. https://doi.org/10.1186/1479-5876-10-224
47. Rattner, A., Yu, H., Williams, J., Smallwood, P. M., & Nathans, J. (2013). Endothelin-2 signaling in the neural retina promotes the endothelial tip cell state and inhibits angiogenesis. Proceedings of the National Academy of Sciences, 110(40), E3830–E3839. https://doi.org/10.1073/pnas.1315509110
48. Richard, A. J., & Stephens, J. M. (2014). The role of JAK-STAT signaling in adipose tissue function. Biochimica et Biophysica Acta, 1842(3), 431–439. https://doi.org/10.1016/j.bbadis.2013.05.030
49. Rosanò, L., Salani, D., Di Castro, V., Spinella, F., Natali, P. G., & Bagnato, A. (2002). Endothelin-1 promotes proteolytic activity of ovarian carcinoma. Clinical Science (London, England: 1979), 103 Suppl 48, 306S–309S. https://doi.org/10.1042/CS103S306S
50. Saita, Y., Yazawa, H., Koizumi, T., Morita, T., Tamura, T., Takenaka, T., & Honda, K. (1998). Mitogenic activity of endothelin on human cultured prostatic smooth muscle cells. European Journal of Pharmacology, 349(1), 123–128. https://doi.org/10.1016/S0014-2999(98)00183-6
51. Sakaguchi, M., Oka, M., Iwasaki, T., Fukami, Y., & Nishigori, C. (2012). Role and Regulation of STAT3 Phosphorylation at Ser727 in Melanocytes and Melanoma Cells. Journal of Investigative Dermatology, 132(7), 1877–1885. https://doi.org/10.1038/jid.2012.45
52. Schindler, C., & Darnell, J. E. (1995). Transcriptional Responses to Polypeptide Ligands: The JAK-STAT Pathway. Annual Review of Biochemistry, 64(1), 621–652. https://doi.org/10.1146/annurev.bi.64.070195.003201
53. Siao, A.-C., Lin, Y.-Y., Shih, L.-J., Tsuei, Y.-W., Chuu, C.-P., Kuo, Y.-C., & Kao, Y.-H. (2020). Endothelin-1 stimulates preadipocyte growth via the PKC, STAT3, AMPK, c-JUN, ERK, sphingosine kinase, and sphingomyelinase pathways. American Journal of Physiology. Cell Physiology. https://doi.org/10.1152/ajpcell.00491.2019
54. Simeone-Penney, M. C., Severgnini, M., Rozo, L., Takahashi, S., Cochran, B. H., & Simon, A. R. (2008). PDGF-induced human airway smooth muscle cell proliferation requires STAT3 and the small GTPase Rac1. American Journal of Physiology-Lung Cellular and Molecular Physiology, 294(4), L698–L704. https://doi.org/10.1152/ajplung.00529.2007
55. Stephens, J. M., Morrison, R. F., & Pilch, P. F. (1996). The Expression and Regulation of STATs during 3T3-L1 Adipocyte Differentiation. Journal of Biological Chemistry, 271(18), 10441–10444. https://doi.org/10.1074/jbc.271.18.10441
56. Sun L, Ma K, Wang H, Xiao F, Gao Y, Zhang W, Wang K, Gao X, Ip N, Wu Z. JAK1-STAT1-STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts. J Cell Biol. 2007 Oct 8;179(1):129-38. doi: 10.1083/jcb.200703184. Epub 2007 Oct 1. PMID: 17908914; PMCID: PMC2064742.
57. Takeda, K., Noguchi, K., Shi, W., Tanaka, T., Matsumoto, M., Yoshida, N., Kishimoto, T., & Akira, S. (1997). Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proceedings of the National Academy of Sciences, 94(8), 3801–3804. https://doi.org/10.1073/pnas.94.8.3801
58. Takeda, Kiyoshi, Kaisho, T., Yoshida, N., Takeda, J., Kishimoto, T., & Akira, S. (2015). Correction: Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. Journal of Immunology (Baltimore, Md. : 1950), 194(7), 3526. https://doi.org/10.4049/jimmunol.1500168
59. Tang, Q.-Q., Otto, T. C., & Lane, M. D. (2003). Mitotic clonal expansion: A synchronous process required for adipogenesis. Proceedings of the National Academy of Sciences, 100(1), 44–49. https://doi.org/10.1073/pnas.0137044100
60. Tang, Y.-C., Liu, C.-W., Chang, H.-H., Juan, C.-C., Kuo, Y.-C., Kao, C.-C., Huang, Y.-M., & Kao, Y.-H. (2014). Endothelin-1 Stimulates Resistin Gene Expression. Endocrinology, 155(3), 854–864. https://doi.org/10.1210/en.2013-1847
61. TIAN, Z., AN, W. ERK1/2 contributes negative regulation to STAT3 activity in HSS-transfected HepG2 cells. Cell Res 14, 141–147 (2004). https://doi.org/10.1038/sj.cr.7290213
62. Tsuda, M., Kohro, Y., Yano, T., Tsujikawa, T., Kitano, J., Tozaki-Saitoh, H., Koyanagi, S., Ohdo, S., Ji, R.-R., Salter, M. W., & Inoue, K. (2011a). JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. Brain, 134(4), 1127–1139. https://doi.org/10.1093/brain/awr025
63. Wang, D., Zhou, Y., Lei, W., Zhang, K., Shi, J., Hu, Y., Shu, G., & Song, J. (2009). Signal transducer and activator of transcription 3 (STAT3) regulates adipocyte differentiation via peroxisome-proliferator-activated receptor gamma (PPARgamma). Biology of the Cell, 102(1), 1–12. https://doi.org/10.1042/BC20090070
64. Wang, N., Verna, L., Hardy, S., Zhu, Y., Ma, K.-S., Birrer, M. J., & Stemerman, M. B. (1999). c-Jun Triggers Apoptosis in Human Vascular Endothelial Cells. Circulation Research, 85(5), 387–393. https://doi.org/10.1161/01.res.85.5.387
65. Wang, R., Löhr, C. V., Fischer, K., Dashwood, W. M., Greenwood, J. A., Ho, E., Williams, D. E., Ashktorab, H., Dashwood, M. R., & Dashwood, R. H. (2012). Epigenetic inactivation of endothelin-2 and endothelin-3 in colon cancer. International Journal of Cancer, 132(5), 1004–1012. https://doi.org/10.1002/ijc.27762
66. Wen, Z., Zhong, Z., & Darnell, J. E. (1995). Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell, 82(2), 241–250. https://doi.org/10.1016/0092-8674(95)90311-9
67. Xiong, Y., Tanaka, H., Richardson, J. A., Williams, S. C., Slaughter, C. A., Nakamura, M., Chen, J. L., & Yanagisawa, M. (2001). Endothelin-1 stimulates leptin production in adipocytes. The Journal of Biological Chemistry, 276(30), 28471–28477. https://doi.org/10.1074/jbc.M103478200
68. Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., & Masaki, T. (1988). A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature, 332(6163), 411–415. https://doi.org/10.1038/332411a0
69. Yanagita, M., Arai, H., Nakano, T., Ohashi, K., Mizuno, K., Fukatsu, A., Doi, T., & Kita, T. (2001). Gas6 Induces Mesangial Cell Proliferation via Latent Transcription Factor STAT3. Journal of Biological Chemistry, 276(45), 42364–42369. https://doi.org/10.1074/jbc.m107488200
70. Yang. (2014). Regulation and function of signal transducer and activator of transcription 3. World Journal of Biological Chemistry, 5(2), 231–239. https://doi.org/10.4331/wjbc.v5.i2.231
71. Zhang, Y., Xu, M., Zhang, X., Chu, F., & Zhou, T. (2018). MAPK/c-Jun signaling pathway contributes to the upregulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL induced by Epstein-Barr virus-encoded BARF1 in gastric carcinoma cells. Oncology Letters. https://doi.org/10.3892/ol.2018.8293
72. Zhu, H., Xu, Y., Gong, F., Shan, G., Yang, H., Xu, K., Zhang, D., Cheng, X., Zhang, Z., Chen, S., Wang, L., & Pan, H. (2017). Reference ranges for serum insulin-like growth factor I (IGF-I) in healthy Chinese adults. PLOS ONE, 12(10), e0185561. https://doi.org/10.1371/journal.pone.0185561
73. Zong, C. S., Chan, J., Levy, D. E., Horvath, C., Sadowski, H. B., & Wang, L.-H. (2000). Mechanism of STAT3 Activation by Insulin-like Growth Factor I Receptor. Journal of Biological Chemistry, 275(20), 15099–15105. https://doi.org/10.1074/jbc.m000089200

指導教授

高永旭(Yung-Hsi Kao)

審核日期

2021-1-21

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