神經系統的發育與受傷反應機制，為現今神經科學研究最重要的範疇。尋找細胞之特有生化標籤，用以標示特殊細胞之變化，為哺乳動物之活體研究中，十分重要的一環。中間絲蛋白與其附屬蛋白（IF / IFAP）為細胞骨骼中相當特殊的一類，其有細胞種類之專一性，在不同種類的細胞，甚至是同一細胞的不同分化時期，都可能會有不同中間絲蛋白的表現。本實驗室發現一特殊之中間絲附屬蛋白IFAP-70/280kD，並由免疫螢光顯微鏡的研究得知，它在體內的表現只侷限於胚胎時期與出生早期的輻射膠細胞與肌肉母細胞（myoblast）內，而通常於出生後一週後此蛋白質之表達即告停止。然而在神經受傷後，此IFAP-70/280kD會再表現，顯示神經系統為因應受傷，而可能重新取得部分其在胚胎時期的能力。據此，本實驗之研究有下列兩方向：

（一） 大白鼠下丘第二級鷹架（secondary scaffold）之研究

下丘（inferiorcolliculus）位於中腦的背側，是聽覺路徑中一個重要的轉驛核（relay nuclei）。對於大白鼠胎鼠發育的研究亦發現，下丘不同時期生成的神經元也有音頻對應排列的關係。然而相關之研究多著重於生理學方面之探討，對於發育期間下丘之形態變化則甚少研究，而且研究之範圍僅限於出生前之胎鼠下丘，研究之方法亦僅止於光學顯微鏡之探討。尤有甚者，對於下丘所含輻射膠細胞及其衍生的神經膠細胞在發有過程中的分化和分佈，至今尚無相關之報告，有待進一步之探討。

（二） 大白鼠神經受傷之研究

高等動物的中樞神經系統(CNS)如果受傷，無論在解剖上或功能上都無法自發地復原。這些死亡的神經元並不會新生，而且早期組織學的研究發現，受傷的神經軸突雖然會再生，但是卻無法穿過在傷口處形成的gliotic scar。然而在PNS中，受傷的神經軸突卻可以再生。但是神經在CNS中無法再重新連結，並非是因為CNS的神經元和PNS的神經元本質上有所不同。已有研究指出，若將CNS的神經細胞移植到PNS的組織中，來自CNS神經的軸突亦能再生。在這兩種組織所產生的不同結果，是由於其不同的"glial environment"造成。

在受傷反應中，星形膠細胞扮演著相當重要的角色。無論是病理性或是物理性的傷害，都會活化星形膠細胞，引發一連串的細胞生理反應，以進行長達數週的修復過程，一般稱之為膠細胞增殖反應，最後則形成一膠細胞疤。Nestin 為一中間絲蛋白質，會在胚胎時期的神經幹細胞與未成熟的星形膠細胞中表現，於出生後成熟星形膠細胞中消失，但在反應型星形膠細胞則會重新出現。本實驗室先前的研究發現，CNS 受傷後，在傷口附近反應型星形膠細胞中，會先有nestin 的再表現，其後才依序觀察到反應型星形膠細胞的增生、變形、移行與結疤等現象。nestin的再表現反應了細胞去分化的過程，其目的在使星形膠細胞進入細胞週期，再行有絲分裂，以因應神經系統受傷回復之需要。目前關於傷口近端反應型星形膠細胞的研究很多，但都侷限在此類細胞本身所具有的各種細胞分子特性，對於引發星形細胞反應的胞外因子所知甚少。先前的研究顯示，血液中的thrombin能促進星形膠細胞增生、變形與激發其thrombin調節素之表現。而且星形膠細胞亦表現各種thrombin受體。近來研究亦指出，thrombin引發星形膠細胞增生反應主要是透過PAR-1 受體，此路徑基本上牽涉Gq 及其下游之MAPK 訊息傳遞路徑。雖然上述研究顯示thrombin可以促進星形膠細胞增生，但是並不能確認它即是一反應型星形膠細胞之誘發因子。因為成熟的星形膠細胞已退出細胞週期，必須先經過去分化過程才能再行有絲分裂，先前研究已知傷口周圍反應型星形膠細胞會表達nestin，乃為其去分化過程必要步驟。是以，有關thrombin如何調控nestin 再表現，為相關研究之重要課題。

(A) 期刊論文

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30. Yang, H.Y. ,* V. Kriho, and G.D. Pappas. 1996. Presence of a 300-kilodalton intermediate filament-associated protein in bovine chromaffin cells. Exp. Neurol., 142: 161-169. (SCI)

31. Kriho, V., G.D. Pappas, N. Lieska , C.M. Wu and H.Y. Yang * 1997. Rat reactive marker (IFAP-70/280kD) is expressed in rat spinal cord motor neurons following transection of sciatic nerve. Proc. Microscopy and Microanalysis 1997, pp.159-160.

32. Yang, H.Y. ,* N. Lieska , V. Kriho, C.M. Wu and G.D. Pappas. 1997. A subpopulation of reactive astrocytes at the immediate site of cerebral cortical injury. Exp. Neurol., 146: 199- 205. (SCI)

33. Huang, B.M., D.M. Stocco, P.H. Li, H.Y. Yang , C.M. Wu and R.L. Norman. 1997. Corticotropin-releasing hormon (CRH) stimulates the expression of the steroidogenic acute regulatory (StAR) protein in MA-1O cells. Biol. Reprod., 57:547-551. (SCI)

34. Kriho, V.K., H.Y. Yang , J.R. Moskal and O. Skalli. 1997. Keratin expression in astrocytomas: an immunofluorescent and biochemical reassessment. Virchows Arch, 431:139-147.

35. Croxtall, J. D., H.L. Wu, H.Y. Yang , B. Smith, C. Sutton, B.I. Chang, G.Y. Shi and R. Flower. 1998. Lipocortin I co-associates with cytokeratins 8 and 18 in A549 cells via the N-terminal domain. Biochim. Biophys. Acta, 1401:39-51. (SCI)

36. Lin, H.H. Lin, T.P. Yang, S.T. Jiang, H.Y. Yang and M.J. Tang. 1999. Bcl-2 overexpression prevents apoptosis-induced Madin-Darby canine kidney simple epithelial cyst formation. Kidney Int., 55:168-178. (SCI)

37. 楊西苑 . 2000. 以生物指標研究臺灣近海烏魚族群的分佈 ( 一 ). 行政院農委會科技計畫研究報告 : 海洋漁業資源調查評估及管理與開發之研究 , pp.276-290.

38. 柯逢春 , 許建宗 , 于宏燦 , 劉健合 , 李忠穎 , 楊西苑 . 2000. 以生物指標研究臺灣近海烏魚族群的分佈 ( 二 ). 行政院農委會科技計畫研究報告 : 漁業技術及資源管理研究 , pp. B70-B83.

39. 許建宗 , 江欣潔 , 劉錫江 , 柯逢春 , 于宏燦 , 劉健合 , 李忠穎 , 楊西苑 . 2000. 以生物指標研究全球海域大目鮪族群之分佈 ( 一 ). 行政院農委會八十九年度試驗研究計畫研究報告 . pp.1-27.

40. 許建宗 , 江欣潔 , 劉錫江 , 柯逢春 , 于宏燦 , 劉健合 , 李忠穎 , 楊西苑 . 2001. 以生物指標研究全球海域大目鮪族群之分佈 ( 二 ). 行政院農委會九十年度試驗研究計畫研究報告 . pp.1-27.

41. Liu, M.Y., H.Y. Lai, B.C. Yang, M.L. Tsai, H.Y. Yang and B.M. Huang. 2001. The inhibitory effects of lead on streoidogenesis in MA-10 mouse Leydig tumor cells. Life Sci., 68:849-859. (SCI)

42. Wu, C.S., S.F. Leu, H.Y. Yang and B.M. Huang. 2001. Melatonin inhibits the expression of steroidogenic acute regulatory protein and steroidogenesis in MA-10 cells. J. Androl., 22: 245-254. (SCI)

43. Huang, B.M., S.F. Leu, H.Y. Yang and R.L. Norman. 2001. Testosteron effects on luteinizing hormone and follicle stimulating hormone responses to gonadotropin-releasing hormone in the mouse. J. Androl., 22: 507-513. (SCI)

44. 柯逢春 , 楊西苑 , 許建宗 , 于宏燦 , 劉健合 . 2001. 以生物指標研究臺灣近海烏魚族群的分佈 ( 三 ). 行政院農委會科技計畫研究報告 : 漁業技術及資源管理研討會 , pp.25-32.

45. 楊西苑 , 江欣潔 , 柯逢春 , 許建宗 . 2002. 全球海域大目鮪族群之分佈 . 行政院農委會漁業署九十年度「鮪、魷漁業資源」計畫研討會報告專輯第五輯 .,pp.16-50.

46. 楊西苑 , 江欣潔 , 許建宗 , 柯逢春 , 劉錫江 , 于宏燦 . 2002. 以生物指標研究全球海域大目鮪族群之分佈 ( 三 ). 行政院農委會漁業署九十一年度科技研究計畫研究報告 . pp.1-28.

47. Liu, M.Y., S.F. Leu., H.Y. Yang and B.M. Huang. 2003. Inhibitory mechanism oflead on sterodiginisis in MA-10 mouse leydig tumor cells. Arc. Androl., 49:29-38.

48. Lee, C.Y., G.D. Pappas, V. Kriho, B.M. Huang, and H.Y. Yang. 2003. Proliferation of reactive astrocytes following needle-insertion lesion in rat brain. Neurol. Res., 25: 767-776. (SCI)

49. Huang, H.C., G.Y. Shi, S.J. Jiang, C.S. Shi, C.M. Wu, H.Y. Yang , and H.L.Wu. 2003. Thrombomodulin-mediated cell adhesion: involvement of its lectin-like domain. J. Biol. Chem., 278: 46750-46759. (SCI)

50. 楊西苑 , 江欣潔 , 許建宗 , 柯逢春 , 劉錫江 , 于宏燦 . 2003. 以生物指標研究全球海域大目鮪族群之分佈 ( 四 ). 行政院農委會漁業署九十二年度科技研究計畫研究報告 . pp.1-33.

51. Lee, H., C.I. Lin, J.J. Liao, Y.W. Lee, H.Y. Yang, C.Y. Lee, H.Y. Hsu, and H.L. Wu. 2004. Lysophospholipids increase ICAM-1 expression in huvec through a G i - and NF- κ -B-dependent mechanism. Am. J. Physiol. Cell Physiol., 287: C1657-C1666. (SCI)

52. Yang. H.Y.* , S.F. Leu, Y.K.Wang, C.S.Wu, and B.M. Huang. 2006. Cordyceps sinensis mycelium induces MA-10 mouse Leydig tumor cell apoptosis by activating the caspase-8 pathway and suppressing the NF-kappaB pathway. Arc. Androl., 52:103-110. (SCI)

53. Lee, T.H., T.H. Chiang, B.M. Huang, T.C.Wang, and H.Y. Yang* . 2006. Ultrastructure of Spermatogenesis of the Paradise Fish, Macropodus opercularis . Taiwania, 51: 170-180.

54. Chiang, H.C., C.C. Hsu, H.D. Lin, G.C. Mac, T.Y. Chiang, and H.Y. Yang* . 2006. Population structure of bigeye tuna ( Thunnus obesus ) in the South China Sea, Philippine Sea and western Pacific Ocean inferred from mitochondrial DNA. Fish. Res., 79:219–225. (SCI)

55. Chiang, H.C., C.C. Hsu, G..C.C.Wu, S.K. Chang, and H.Y. Yang* . 2008. Population structure of bigeye tuna ( Thunnus obesus ) in the Indian Ocean inferred from mitochondrial DNA. Fish. Res. 90:305-312. (SCI)

56. Wu, H.L., C.I. Lin, Y.L. Huang, P.S. Chen, C.H. Kuo, M.S. Chen, G.C.C.Wu, G.Y. Shi, H.Y. Yang* , and H. Lee. 2008. Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells. Biochem. Biophys. Res. Commun., 367:162-168. (SCI)

57. Huang, Y.L., G.Y. Shi, M.J. Jiang, H. Lee, Y.W. Chou, H.L. Wu and Yang H.Y.* 2008. Epidermal growth factor up-regulates the expression of nestin through the Ras-Raf-ERK signaling axis in rat vascular smooth muscle cells. Biochem. Biophys. Res. Commun., 377:361-366. (SCI)

58. Wu, G.C.C., H.C. Chiang, K.S. Chen, C.C. Hsu, and H.Y. Yang* . 2009. Population structure of albacore (Thunnus alalunga) in the Northwestern Pacific Ocean inferred from mitochondrial DNA. Fish. Res., 95:125-131. (SCI)

59. Huang, Y.L., G.Y. Shi, P.H. Su, H. Lee, B.M. Huang, H.L. Wu and H.Y. Yang.* 2009. Thrombin induces nestin expression via the transactivation of EGFR signalings in rat vascular smooth muscle cells. Cell Signal., 21:954-968. (SCI)

60. Huang, Y.L., G.Y. Shi, G.C.C.Wu, H. Lee, M.J. Jiang, H.L.Wu and H.Y. Yang.* Nestin serves as a prosurvival determinant that links to the cytoprotective effect of epidermal growth factor in rat vascular smooth muscle cells. (J. Biochem., 2009, in revision )

61. Wang, T.C., P.H. Su, B.M. Huang, and H.Y. Yang* . The expression of nestin delineates skeletal muscle differentiation in developing rat esophagus. (in preparation)

62. Chiang, H.C., G.C.C.Wu, K.S. Chen, C.C. Hsu and H.Y. Yang* . Phylogeography and population structure of global bigeye tuna (Thunnus obesus) inferred from mitochondrial DNA. (in preparation)

(B) 研討會論文 （ 1999 –2008 ）

1. Wu, C.S., J.I. Chuang, S.F. Leu, H.Y. Yang and B.M. Huang. 1999. Melatonin inhibits the expression of steroidogenic acute regulatory protein and steroidgenesis in MA-10 cells. The 14th Joint Ann. Conf. Biomed. Sci.

2. Liu, M.Y., H.Y. Lai, B.C. Yang, M.L. Tsai, H.Y. Yang and B.M. Huang. 1999 Inhibitory mechanism of lead on mouse Leydig tumor cell steroidogenesis. The 14th Joint Ann. Conf. Biomed. Sci.

3. Wu, C.S., C.I. Chuang, S.F. Leu, H.Y. Yang , B.M. Huang. 1999. Melatonin inhibits the expression of steroidogenic acute regulatory protein and sterodogenesis in MA-10 cells. Society for the Study of Reproduction, 32th annual meeting, Pullman , Washington , USA .

4. Lee, C.Y., C.M.Wu, B.M. Huang and H.Y. Yang* . 2000. Immunohistochemical studies on the proliferation of reactive astrocytes following stab injury in rat brain. The 15th Joint Ann. Conf. Biomed. Sci. p. 223.

5. 楊西苑 * 、劉錫江、許建宗、柯逢春、于宏燦、劉健合 . 2000. 以生物指標研究全球海域大目鮪族群之分佈 . 行政院農委會漁業署八十八年下半年及八十九年度遠洋漁業資源調查評估及管理與開發之研究期中報告 . p15.

6. 柯逢春、許建宗、 楊西苑 、于宏燦 . 2000. 以生物指標研究臺灣近海烏魚族群的分布 . 行政院農委會漁業署八十八年下半年及八十九年度科技計畫期中報告 . p. 16.

7. Lee, C.Y., G.D. Pappas, V. Kriho, C.M.Wu, and H.Y. Yang* . 2000. Proliferation of a subpopulation of reactive astrocytes following needle-insertion lesion in rat brain. Soc. Neurosci. Abstr. 26:513.

8. 許建宗、江欣潔、劉錫江、于宏燦、劉健合、 楊西苑 * . 2000. 以生物指標研究全球海域大目鮪族群之分佈 . 台灣水產學會 2000 年會 , O-97.

9. 柯逢春、許建宗、于宏燦、劉健合、 楊西苑 * . 2000. 以生物指標研究臺灣近海烏魚族群的分布 . 台灣水產學會 2000 年會 , O-98.

10. 江亭萱、李宗翰、黃步敏、林錦燕、湯致遠、 楊西苑 * . 2000. 蓋斑鬥魚精巢之超微結構 . 台灣水產學會 2000 年會 , P-74.

11. Liu. C., G.D. Pappas, V. Kriho, B.M. Huang and H.Y. Yang* . 2001. Expression of IFAP-70/280kD in large neurons of rat dorsal root ganglia. Supplement to Molecular Biology of the Cell, 12: 185a -186a .

12. Hsu F.H., C.Y. Lee, C. Liu, B.M. Huang and H.Y. Yang* . 2002. Expression of IFAP-70/280kD a in the spinal cord meurons of adult rat. The 17th Joint Ann. Conf. Biomed. Sci. p141.

13. Liu. C., C.Y. Lee, Y.W. Lo, B.M. Huang and H.Y. Yang* . 2002. Expression of IFAP-70/280kD in a subpopulation of large neurons of rat dorsal root ganglia. The 17th Joint Ann. Conf. Biomed. Sci. p141.

14. 江欣潔、許建宗、柯逢春、劉錫江、于宏燦、 楊西苑 *. 2002. 以生物指標研究全球海域大目鮪族群之分佈 . 台灣水產學會 2002 年會 , C-4-1.

15. 楊西苑 *, 江欣潔 , 柯逢春 , 許建宗 . 2002. 全球海域大目鮪族群之分佈 . 行政院農委會漁業署九十年度「鮪、魷漁業資源」計畫研討會報告專輯第五輯 .,pp.16-50. （經費由農委會 91 農科 - 2.5.2 - 漁 -F1(3) 補助）

16. 江欣潔、許建宗、劉錫江、 楊西苑 *. 2003. 全球大目鮪族群分佈研究 . 九十二年度行政院農委會漁業署委辦鮪、魷漁業資與漁業現況研討會 , p26. （經費由農委會 92 農科 - 9.1.2 - 漁 -F1(6) 補助）

17. 江欣潔、許建宗、林弘都、柯逢春、馬國欽、 楊西苑 *. 2004. 以粒線體 DNA 控制區序列分析建立西太平洋與東大西洋大目鮪之族群遺傳結構 . 台灣水產學會九十三年度會員大會暨學術論文發表會 .

18. 江欣潔、許建宗、林弘都、柯逢春、馬國欽、蔣鎮宇、 楊西苑 *. 2005. 西太平洋大目鮪族群結構之研究 . 海峽兩岸魚類學研討會 . 中華民國魚類學會主辦 . pp.50

19. Chiang H.C., C.C. Hsu, H.D. Lin, F.C. Ke, G.C. Ma, T.Y. Chiang, and H.Y. Yang*. 2005. Mitochondrial DNA analyses of western Pacific bigeye tuna

(Thunnus obesus) population structure in the South China Sea , Philippines Sea and western Pacific Ocean . The 7 th Indo-Pacific Fish Conference. pp.137.

20. 江欣潔、許建宗、何杰騰、張水鍇、 楊西苑 *. 2006. 以粒線體 DNA 控制區序列分析建立印度洋大目鮪族群結構之研究 . 台灣水產學會九十五年度會員大會暨學術論文發表會 . pp.159.

21. 何杰騰、許建宗、陳國書、吳慶明、江欣潔、 楊西苑 *. 2006. 以粒線體基因探討太平洋西北區域的長鰭鮪之族群遺傳結構 . 台灣水產學會九十五年度會員大會暨學術論文發表會 . pp.160.

22. Su. P.H., T.C.Wang, Y.L. Huang, G.C.C.Wu, and H.Y. Yang * 2006. Expression of plectin in the developing rat spinal cord, 第二十一屆生物醫學聯合學術年會，論文編號 P644 ( 此論文獲得優良看板論文競賽獎 )

23. Chiang H.C., C.C. Hsu, G.C.C.Wu, S.K. Chiang, and H.Y. Yang* . 2007. Bigeye tuna (Thunnus obesus) in the Indian Ocean are composed of a single

panmictic population. 台灣地球科學聯合學術研討會，論文編號 PP-615

24. Wu G.C.C., H.C. Chiang, C.C. Hsu, and H.Y. Yang*. 2007. Albacore (Thunnus alalunga) in the Northwestern Pacific are composed of two distinct clades. 台灣地球科學聯合學術研討會，論文編號 PP-616

25. Huang Y.L., P.H. Su, T.C.Wang, Y.W. Chou, and H.Y. Yang* 2008. EGF-induced phenotypic modulation of vascular smooth muscle cells through the regulation of nestin expression. 15th International Vascular Biology Meeting. P116

26. 吳卓臻 , 周耀文 , 江欣潔 , 陳志遠 , 許建宗 , 楊西苑 , 2008 。以粒線體 DNA 控制區序列分析建立西太平洋與西印度洋黃鰭鮪族群結構之研究。中華民國魚類學會年會暨研討會 , pp.77 。

27. 江欣潔 , 吳卓臻 , 陳國書 , 周耀文 , 許建宗 , 楊西苑 , 2008 。 全球大目?族群 結構與親緣地理學之研究。中華民國魚類學會年會暨研討會 , pp.76 。

28. Huang Y.L., P.H. Su, G.C.C.Wu, T.C.Wang, Y.W. Chou, K.W. Chang, H.Y. Yang* 2008. EGF-induced Phenotypic Modulation and Cytoprotective Effect in Vascular Smooth Muscle Cells through the Regulation of Nestin Expression. 4 th International Symposium of the Kanagawa University - National Taiwan University Exchange Program. P9