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楊春茂

 

楊春茂 (Chuen-Mao Yang)

職稱:教授

研究室:細胞分子藥理實驗室

最高學歷Ph.D.

學校/國家:密州大學醫學院藥理/毒理研究所/美國

分機號碼5123

電子郵件帳號 chuenmao@mail.cgu.edu.tw

個人網頁網址http://163.25.114.16/chuen-mao/index.htm

是否直接連接至個人網頁:是

研究室現有: 博士後研究員  1

博士班研究生 3

碩士班研究生 4

專任研究助理  3

大學部專題生    

 

研究方向及研特色

    本研究室主要針對與發炎性疾病之生理、藥理及病理致病機轉做探討,最近幾年我們

進一步利用已建立的研究模式及經驗,應用來探討腦部神經退化的病理機轉。我們首先探

討在各種不同因子與細菌感染誘導發炎標的蛋白表現的機轉,可以作為未來這些疾病治療

及新藥開發的參考與應用。

 

   1. 發炎標的蛋白的表現與神經退化及發炎疾病的關係:

因為在腦部傷害,如外傷、感染或中風等,其間許多因子也會大量生成,故探討其對

腦部傷害(發炎及退化)之影響亦是我們研究的一大主題。同時參與國科會神經科學先

導計畫,我們探討許多發炎疾病的危險因子如:日本腦炎病毒感染、凝血酶、BK

oxLDLIL-1bLTAET-1 TGF-b1及高濃度葡萄糖在中樞神經系統的星狀神經膠

細胞和神經原細胞中誘導發炎標的蛋白質表現的機轉與腦部發炎的關係。我們陸續證

實在鼠腦RBA-1細胞與人類神經瘤母細胞SK-N-SH中包括日本腦炎病毒感染、凝血

酶、BKoxLDLIL-1bLTAET-1 TGF-b1及高濃度葡萄糖誘發MMP-9COX-2

cPLA2表現之機轉及其影響細胞遷移的作用,這些刺激因子可藉由NADPH氧化

酶、活性氧分子、 MAPKPI3K等路徑促使NF-kBAP-1Nrf2活化而誘發MMP-9

COX-2cPLA2的表現。了解這些調控機轉將是未來研發腦部抗發炎藥物之基本依

據。

 

 

 The mechanisms of pro-inflammatory factors-stimulated activation of various signaling molecules and transcription factors leading to expression of MMP-9 in brain astrocytes and human neuroblastoma. Pro-inflammatory mediators stimulate respective signaling pathways leading to activation of transcription factors such as NF-kB, AP-1, or Elk-1. Ultimately, up-regulation of MMP-9 may contribute to the pathogenesis of several neurodegenerative diseases.

    2. 發炎標的蛋白的表現與動脈粥狀硬化疾病的關係:

目前動脈粥狀硬化被認為是一種發炎的疾病。從文獻上已知G protein-coupled receptors (GPCRs)的致效劑(BK, Thrombin, ATP)、生長因子、ox-LDLSphigosine 1-phosphate可以造成慢性血管內皮的損傷及血管內膜平滑肌細胞的增生,與誘發各種發炎標的蛋白cPLA2COX-2VCAM-1ICAM-1MMP-9的表現,這些現象可能在動脈粥狀硬化的病理機轉扮演重要的角色。在血管平滑肌方面證實,發炎因子可以經由活化

42/p44 MAPKp38 MAPKNF-kB等訊號分子調控發炎基因cPLA2COX-2VCAM-1ICAM-1MMP-9的表現。

     3. 發炎標的蛋白的表現與風濕性關節炎疾病的關係:

發炎反應亦是風濕性關節炎疾病的主要病徵。在實驗與臨床上此疾病發展過程中多種發炎蛋白如黏著分子、COX-2cPLA2及其產物的表現都有增加的情形,這些發炎蛋白的表現所引發的發炎機轉可能促使組織重塑並加劇發炎反應。另外,因產生活性氧分子(例如粒線體失能和NAPDH 氧化酶活化)而形成的氧化壓力也可能和風濕性關節炎反應有密切的相關性。細胞產生活性氧分子並啟動細胞內訊號傳遞路徑而增強慢性發炎反應。滑液膜纖維母細胞受到LPSIL-1bTNF-a刺激經由活化MAPKs (p42/p44 MAPKJNK1/2p38 MAPK)轉活化Src、生長因子受體(EGFRPDGFR)PI3K/Aktc-Src/NADPH oxidase/MAPKs啟動轉錄因子NF-kBAP-1導致p300聚集至標的基因,誘發cPLA2COX-2VCAM-1ICAM-1的表現而造成淋巴球與細胞的黏著作用及PGs的產生。另外,cytokines可以透過c-Src/NADPH oxidase/MAPKs/Nrf2的訊號途徑,活化Nrf2轉移到細胞核,啟動HO-1基因的轉錄作用,合成HO-1抑制這些發炎標的蛋白的表現,具有保護風濕性關節炎、抗發炎的作用。

4. 發炎標的蛋白的表現與呼吸道和肺部疾病的關係:

發炎反應是所有主要呼吸道疾病如氣喘與慢性肺部阻塞性疾病的一項病徵。在臨床及實驗上的呼吸道疾病可發現多種發炎蛋白例如黏附分子、環氧化酶及其產物、細胞激素與基質金屬蛋白酶(MMPs)有濃度增加的趨向,此外在實驗動物身上則顯示這幾種發炎標的蛋白促成肺部疾病。尤其是細胞激素(IL-1bTNF-b)、內毒素以及香菸燃燒物質(CS)與呼吸道發炎有密切關係。這些發炎蛋白表現所引發常見的發炎作用機轉可能會促進組織重塑及使發炎反應加劇。氣管平滑肌細胞與表皮細胞是呼吸道參與免疫反應及發炎的重要器官。受到 cytokines、細菌感染與香菸萃取物的刺激會引發 cPLA2 COX-2 的表現及 PGs 的合成增加、誘發大量表現黏著分子而促進血球聚集到發炎的位置及促進細胞間的結合能力、誘發基質金屬蛋白酶(MMPs) 的表現,使得 extracellular matrix (ECM) 的分解,MMPs在細胞移行、增生及組織重塑與呼吸道發炎的病理機轉扮演重要的角色。cytokines、細菌感染與香菸萃取物可以透過活化各種訊號傳遞途徑而誘導發炎標的蛋白的表現,導致發炎的惡化,是造成呼吸道發炎的重要因素。呼吸道受到氧化壓力的刺激產生大量的ROS 是一種重要的發炎因子。在氣管平滑肌細胞上,香菸萃取液經由活化c-Src/NADPH oxidase/MAPKs/Nrf2 的訊號途徑,活化Nrf2轉移到細胞核,啟動HO-1 基因的轉錄作用合成HO-1, 對抗呼吸道發炎的作用。總結而論,這些發炎蛋白表現所引發常見的發炎作用機轉可能會促進組織重塑及使發炎反應加劇。

 

General overview of the inflammatory signaling pathways in respiratory diseases. Many of the known inflammatory target proteins, such as MMP-9, ICAM-1, VCAM-1, COX-2, and cPLA2, are associated with inflammatory signaling pathways induced by various stimuli, including TNF-a, IL-1b, ATP, cigarette smoke, LTA, or LPS. Moreover, the SFKs, PKCs, growth factor tyrosine kinase receptors, NADPH oxidase/ROS, PI3K/Akt, MAPKs are components of signaling cascades that respond to extracellular stimuli by targeting transcription factors, such as NF-kB and AP-1, resulting in the modulation of inflammatory gene expression associated with pulmonary diseases.

 

 

 

最近五年所發表論文:*代表通訊作者

1. Hsieh, H.L., H.H. Wang, C.Y. Wu, W.H. Tung, and C.M. Yang.* Lipoteichoic acid induces matrix metalloproteinase-9 expression via transactivation of PDGF receptors and NF-kB activation in rat brain astrocytes. Neurotoxicity Res. 17:344–359, 2010, May. Neuroscience, 89/252=35.32%, IF=3.538.

2. Luo, S.F., Y.Y. Fang, H.L. Hsieh, P.L. Chi, C.C. Lin, L.D. Hsiao, C.C. Wu, J.S. Wang, and C.M. Yang.* Involvement of MAPKs and NF-kB in TNF-a-induced VCAM-1 expression in human rheumatoid arthritis synovial fibroblasts. Arthritis & Rheumatism, 62:105-116, 2010, Jan. Rheumatology, 3/32=9.38%, IF=7.764.

3. Tung, W.H., H.L. Hsieh, and C.M. Yang.* Enterovirus 71 induces COX-2 expression via MAPKs, NF-κB, and AP-1 in SKNSH cells: Role of PGE2 in viral replication. Cell. Signal. 22:234-246, 2010, Feb. Cell Biology, 65/184=35.33%, IF=4.315.

4. Wang, H.H., H.L. Hsieh, C.Y. Wu, and C.M. Yang.* Oxidized low-density lipoprotein-induced matrix metalloproteinase-9 expression via PKC-d/p42/p44 MAPK/Elk-1 cascade in brain astrocytes. Neurotox. Res. 17:50–65, 2010, Jan. Neuroscience, 89/252=35.32%, IF=3.538.

5. Lin, C.C., I.T. Lee, Y.L. Yang, C.W. Lee, Y. R. Kou, and C.M. Yang.* Induction of COX-2/PGE2/IL-6 is crucial for cigarette smoke extract-induced airway inflammation: role of TLR4-dependent NADPH oxidase activation. Free Radical. Biol. Med. 48:240-254, 2010, Jan.  ENDOCRINOLOGY & METABOLISM, 16/128=12.5%, IF= 5. 736.

6. Jou, M.J., T.I. Peng, L.F. Hsu, S.B. Jou, R.J. Reiter, C.M. Yang, C.C. Chiao, Y.F. Lin, and C.C. Chen. Visualization of melatonin's multiple mitochondrial levels of protection against mitochondrial Ca-mediated permeability transition and beyond in rat brain astrocytes. J. Pineal Res. 48:20-38, 2010, Jan. Neuroscience, 13/252=5.16%, IF= 7.227.

7. Wu, C.Y., P.L. Chi, H.L. Hsieh, S.F. Luo, and C.M. Yang.* TLR4-Dependent Induction of Vascular Adhesion Molecule-1 in Rheumatoid Arthritis Synovial Fibroblasts: Roles of Cytosolic Phospholipase A2a/Cyclooxygenase-2. J. Cell. Physiol. 223:480-491, 2010, May. Physiology, 15/83=18.07%, IF=3.839.

8. Lee, I.T., C.W. Lee, W.H. Tung, S.W. Wang, C.C. Lin, J.C. Shu, and C.M. Yang.* Cooperation of TLR2 with MyD88, PI3K, and Rac1 in lipoteichoic acid-induced cPLA2/COX-2-dependent airway inflammatory responses. Am. J. Pathol. 176:1671-1684, 2010, Apr. Pathology, 9/75=12%, IF=4.591.

9. Lee, C.W. I.T. Lee, C.C. Lin, H.C. Lee, W.N. Lin, and C.M. Yang.* Activation and induction of cytosolic phospholipase A2 by IL-1b in human tracheal smooth muscle cells: Role of MAPKs/p300 and NF-kB. J. Cell. Biochem. 109:1045-1056, 2010, Apr. Biochemistry & Molecular Biology, 107/289=37.02%, IF=3.263.

10. Cheng, C.Y., C.T. Kuo, C.C. Lin, H.L. Hsieh, and C.M. Yang.* IL-1b induces expression of matrix metalloproteinase-9 and cell migration via a c-Src-dependent, growth factor receptor transactivation in A549 cells. Br. J. Pharmacol. 160:1595-1610, 2010, Aug. Pharmacology, 24/254=9.45%, IF=4.842.

11. Chu P.H., H.I. Yeh , H.H. Wu , R.C. Hong, T.F. Shiu, and C.M. Yang. Deletion of the FHL2 gene attenuates the formation of atherosclerotic lesions after a cholesterol-enriched diet. Life Sci. 86: 365371, 2010, Feb. Medicine, Research & Experimental, 53/123=48.39%, IF=2.702.

12. Tung, W.H., I.T. Lee, H.L. Hsieh, and C.M. Yang.* EV71 induces COX-2 expression via c-Src/PDGFR/PI3K/Akt/p42/p44 MPAK/AP-1 and NF-kB in rat brain astrocytes. J. Cell. Physiol. 224: 376–386, 2010, Aug. Physiology, 15/83=18.07%, IF=3.839.

13. Lee, I.T., C.C. Lin, Y.C. Wu, and C.M. Yang.* TNF-a induces matrix metalloproteinase-9 expression in A549 cells: Role of TNFR1/TRAF2/PKCa-dependent signaling pathways. J. Cell. Physiol. 224:454-464, 2010. Physiology, 15/83=18.07%, IF=3.839.

14. Cheng, S.E., I.T. Lee, C.C. Lin, Y. R. Kou, and C.M. Yang.* Cigarette smoke particle phase extract induces HO-1 expression in human tracheal smooth muscle cells: Role of c-Src/NADPH oxidase/MAPKs/Nrf2 signaling pathway. Free Radical Biol. Med. 48:14101422, 2010, May. ENDOCRINOLOGY & METABOLISM, 16/128=12.5%, IF= 5. 736.

15. Yang, C.M.,* S.F. Luo, H.L. Hsieh, P.L. Chi, C.C. Lin, C.C. Wu, and L.D. Hsiao. Interleukin-1b Induces ICAM-1 Expression Enhancing Leukocyte Adhesion in Human Rheumatoid Arthritis Synovial Fibroblasts: Involvement of ERK, JNK, AP-1 and NF-kB. J. Cell. Physiol. 224:516-526.  2010, Aug. Physiology, 15/83=18.07%, IF=3.839.

16. Wang, H.H., H.L. Hsieh, C.Y. Wu and C.M. Yang.* Endothelin-1 enhances cell migration via matrix metalloproteinase-9 up-regulation in brain astrocytes. J. Neurochem. 113:1133-1149, 2010, Jun. Neuroscience, 55/252=21.83%, IF= 4.281.

17. Shih, R.H., S.E. Cheng, W.H. Tung, and C.M. Yang.* Up-regulation of heme oxygenase-1 protects against cold injury-induced brain damage: a laboratory-based study. J. Neurotrauma, 27:1477-1487. 2010, Aug. Neuroscience, 76/252=30.16%, IF=3.714.

18. Hsieh, H.L., H.H. Wang, C.Y. Wu, and C.M. Yang.* ROS-dependent c-Fos/AP-1 induction up-regulates heme oxygenase-1 expression by bradykinin in brain astrocytes. Antioxidants Redox Signal. 13:1829–1844, 2010, Dec. Biochemistry & Molecular Biology, 27/289=9.34%, IF=7.407.

19. Shih, R.H., I.T. Lee, H.L. Hsieh, Y.R. Kou, and C.M. Yang.* Cigarette smoke extract induces HO-1 expression in mouse cerebral vascular endothelial cells: Involvement of c-Src/NADPH oxidase/PDGFR/JAK2/STAT3 pathway. J. Cell. Physiol. 225:741-750, 2010, Nov. Physiology, 15/83=18.07%, IF=3.839.

20. Tung, W.H., H.W. Tsai, I.T. Lee, H.L. Hsieh, W.J. Chen, Y.L. Chen, and C.M. Yang.* Japanese encephalitis virus induces matrix metalloproteinase-9 in rat brain astrocytes via NF-κB signalling dependent on MAPKs and reactive oxygen species. Br. J. Pharmacol. 161:1566-1583, 2010, Dec. Pharmacology, 24/254=9.45%, IF=4.842.

21. Wang, H.H., H.L. Hsieh, and C.M. Yang.* Calmodulin kinase II-dependent transactivation of PDGF receptors mediates astrocytic MMP-9 expression and cell motility induced by lipoteichoic acid. J. Neuroinflammation, 7:84, 2010, Nov. Neuroscience, 32/252=12.7%, IF=5.408.

22. Shih, R.H. and C.M. Yang.*Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced cyclooxygenase-2 expression in mouse brain endothelial cells. J. Neuroinflammation, 7:86, 2010, Nov. Neuroscience, 32/252=12.7%, IF=5.408.

23. Hsieh, H.L., H.H. Wang, W.B. Wu, P.J. Chu, and C.M. Yang.* Transforming growth factor-b1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-kB pathways. J. Neuroinflammation, 7:88, 2010, Dec. Neuroscience, 32/252=12.7%, IF=5.408.

24. Tung, W.H., H.L. Hsieh, I.T. Lee, and C.M. Yang.* Enterovirus 71 modulates a COX-2/PGE2/cAMP-dependent viral replication in human neuroblastoma cells: Role of the c-Src/EGFR/p42/p44 MAPK/CREB signaling pathway. J. Cell. Biochem. 112:559-570, 2011, Feb. Biochemistry & Molecular Biology, 107/289=37.02%, IF=3.263.

25. Cheng, S.E., C.C. Lin, I.T. Lee, C.K. Hsu, Y. R. Kou, and C.M. Yang.* Cigarette smoke extract regulates cytosolic phospholipase A2 expression via NADPH oxidase/MAPKs/AP-1 and p300 in human tracheal smooth muscle cells. J. Cell. Biochem. 112:589-599, 2011, Feb. Biochemistry & Molecular Biology, 107/289=37.02%, IF=3.263.

26. Lee, C.W., C.C. Lin, I.T. Lee, H.C. Lee, and C.M. Yang.* Activation and induction of cytosolic phospholipase A2 by TNF-a mediated through Nox2, MAPKs, NF-kB, and p300 in human tracheal smooth muscle cells. J. Cell. Physiol. 226:2103-2114, 2011, Aug. Physiology, 15/83=18.07%, IF=3.839.

27. Wang, H.H., H.L. Hsieh, and C.M. Yang.* Nitric oxide production by endothelin-1 enhances astrocytic migration via the tyrosine nitration of matrix metalloproteinase-9. J. Cell. Physiol. 226:2244-2256, 2011, Sep. Physiology, 15/83=18.07%, IF=3.839.

28. Lin, W.N., C.C. Lin, Cheng, S.E., and C.M. Yang.* Regulation of COX-2 and cPLA2 Gene Expression by LPS through the RNA-binding Protein HuR: Involvement of NADPH oxidase, ROS and MAPKs. Br. J. Pharmacol. 163:1691-1706, 2011, Aug. Pharmacology, 24/254=9.45%, IF=4.842.

29. Tung, W.H., H.L. Hsieh, I.T. Lee, and C.M. Yang.* Enterovirus 71 induces integrin β1/EGFR-Rac1-dependent oxidative stress in SK-N-SH cells: Role of HO-1/CO in viral replication. J. Cell. Physiol. 226:3316-3329, 2011, Dec. Physiology, 15/83=18.07%, IF=3.839.

30. Liang CJ, CP Tseng, C.M. Yang, and YH Ma. 20-Hydroxyeicosatetraenoic acid inhibits ATP-induced COX-2 expression via peroxisome proliferator activator receptor-α in vascular smooth muscle cells. Br. J. Pharmacol. 163:815-825, 2011, Jun. Pharmacology, 24/254=9.45%, IF=4.842.

31. Chi, P.L., S.F. Luo, H.L. Hsieh, I.T. Lee, L.D. Hsiao, Y.L. Chen, and C.M. Yang.* cPLA2 induction and PGE2 release by IL-1b via the MyD88-dependent and cooperation of p300, Akt, and NF-kB pathway in human rheumatoid arthritis synovial fibroblasts. Arthritis & Rheumatism, 63:2905-2917, 2011, Oct. Rheumatology, 3/32=9.38%, IF=7.764.

32. Shih, R.H., S.E. Cheng, L.D. Hsiao, Y.R. Kou, and C.M. Yang.* Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells. J. Neuroinflammation, 8:104, 2011, Aug. Neuroscience, 32/252=12.7%, IF=5.408.

33. Cheng, C.Y., H.C. Tseng, and C.M. Yang.* Bradykinin-mediated cell proliferation depends on transactivation of EGF receptor in corneal fibroblasts. J. Cell. Physiol. 227:1367-1381, 2012, Apr. Physiology, 15/83=18.07%, IF=3.839.

34. Lin, C.C., W.N. Lin, S.E. Cheng, W.H. Tung, H.H. Wang, and C.M. Yang.* Transactivation of EGFR/PI3K/Akt involved in ATP-induced inflammatory protein expression and cell motility. J. Cell. Physiol. 227:11628-11638, 2012, Apr. Physiology, 15/83=18.07%, IF=3.839.

35. Chi, P.L., Y.W. Chen, L.D. Hsiao, Y.L. Chen, and C.M. Yang.* Heme oxygenase-1 attenuates IL-1b-induced cPLA2 expression via a decrease in NADPH oxidase/ROS/AP-1 activation in human rheumatoid arthritis synovial fibroblasts. Arthritis & Rheumatism, 64:2114-2125, 2012, Jul. Rheumatology, 3/32=9.38%, IF=7.764.

36. Yang, C.M.,* C.C. Lin, I.T. Lee, Y.H. Lin, Caleb M. Yang, W.J. Chen, M.J. Jou and L.D. Hsiao. Japanese encephalitis virus induces matrix metalloproteinase-9 expression via ROS/Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes. J. Neuroinflamamtion. 9:12, 2012, Jan. Neuroscience, 32/252=12.7%, IF=5.408.

37. Cheng, C.Y., H.L. Hsieh, L.D. Hsiao, and C.M. Yang.* PI3-K/Akt/JNK/NF-kB is essential for MMP-9 expression and outgrowth of human limbal epithelial cells on intact amniotic membrane. Stem Cell Res. 9:9-23, 2012, Jul. Cell Biology, 75/184=40.76%, IF=3.693.

38. Hsieh, H.L., C.C. Lin, R.H. Shih, L.D. Hsiao and C.M. Yang.* NADPH oxidase-derived redox signal contributes to lipoteichoic acid-induced MMP-9 regulation in brain astrocytes. J. Neuroinflamamtion, 9:110, 2012, Jul. Neuroscience, 32/252=12.7%, IF=5.408.

39. Lee, I.T. and C.M. Yang.* Role of NADPH oxidase/ROS in pro-inflammatory mediators-induced airway and pulmonary diseases. Biochem Pharmacol. 84:581-590, 2012, Sep. (Review paper). Pharmacology/Pharmacy, 23/254=9.1%, IF=5.009.

40. Hsieh, H.L., C.C. Lin, H.J. Chan, Caleb M. Yang and C.M. Yang.* c-Src-dependent EGF receptor transactivation contributes to ET-1-induced COX-2 expression in brain microvascular endothelial cells. J. Neuroinflammation. 9:152, 2012, Jul. Neuroscience, 32/252=12.7%, IF=5.408.

41. Lin, C.C., I.T. Lee, W.L. Wu, W.N. Lin, and C.M. Yang.* Adenosine triphosphate regulates NADPH oxidase activity leading to hydrogen peroxide production and COX-2/PGE2 expression in A549 cells. Am J Physiol Lung Cell Mol Physiol. 330:L401-L412, 2012, Sep. Physiology, 14/83=16.87%, IF=4.080.

42. Lin, C.C., H.L. Hsieh, R.H. Shih, P.L. Chi, S.E. Cheng, J.C. Chen, and C.M. Yang.* NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes. Cell Communication & Signaling. 10:35, 2012, Nov. Cell Biology, 90/184=48.91%, IF=3.378.

43. Lee, I.T., R.H. Shih, C.C. Lin, J.T. Chen, and C.M. Yang.* Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells. Cell Communication & Signaling, 10:33, 2012, Nov. Cell Biology, 90/184=48.91%, IF=3.378.

44. Lee, I.T., C.C. Lin, C.Y. Lee, P.W. Hsieh, and C.M. Yang.* Protective effects of (-)-epigallocatechin-3-gallate against TNF-a-induced lung inflammation via ROS-dependent ICAM-1 inhibition. J. Nutr. Biochem. 24:124-136, 2013, Jan. Nutrition & Diebetics, 14/77=18.18%, IF=3.794.

45. Cheng S.E., I.T. Lee, C.C. Lin, W.L. Wu, L.D. Hsiao, and C.M. Yang.* ATP Mediates NADPH oxidase/ROS generation and COX-2/PGE2 expression in A549 cells: Role of P2 receptor-dependent STAT3 activation. Plos One, 8:e54125, 2013, Jan. Multidisciplinary Sciences, 8/56=40.29%, IF= 3.234.

46. Yang C.M.,* H.L. Hsieh, C.C. Lin, R.H. Shih, P.L. Chi, S.E. Cheng, and L.D. Hsiao. Multiple factors from BK-challenged astrocytes contribute to the neuronal apoptosis: Involvement of astroglial ROS, MMP-9, and HO-1/CO system. Mol. Neurobiol. 47:1020-1033, 2013, Jun. Neuroscience, 36/252=14.29%, IF=5.137.

47. Lin, C.C., H.L. Hsieh, R.H. Shih, P.L. Chi, S.E. Cheng, and C.M. Yang.* Up-regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-kB pathway in brain microvascular endothelial cells. Cell Communication & Signaling, 11:8, 2013, Jan. Cell Biology, 90/184=48.91%, IF=3.378.

48. Lee I.T., C.C. Lin, C.H. Wang, W.J. Cherng, J.S. Wang, and C.M. Yang.* ATP stimulates PGE2/cyclin D1-dependent VSMCs proliferation via STAT3 activation: role of PKCs-dependent NADPH oxidase/ROS generation. Biochem. Pharmacol. 85:954-964, 2013, Apr. Pharmacology/Pharmacy, 23/254=9.1%, IF=5.009.

49. Yang C.M.,*  I.T. Lee, C.C. Lin, C.H. Wang, W.J. Cherng, and L.D. Hsiao. c-Src-dependent MAPKs/AP-1 activation is involved in TNF-a-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells. Biochem. Pharmacol. 85:1115-1123, 2013, Apr. Pharmacology/Pharmacy, 23/254=9.1%, IF=5.009.

50. Tseng, H.C., I.T. Lee, C.C. Lin, P.L. Chi, S.E. Cheng, R.H. Shih, L.D. Hsiao, and C.M. Yang.* IL-1b promotes corneal epithelial cell migration by increasing MMP-9 expression through NF-kB- and AP-1-dependent pathways. Plos One, 8:e57955 2013, Mar. Multidisciplinary Sciences, 8/56=14029%, IF= 3.234.

51. Yen, F.L., M.H. Tsai, C.M. Yang, C.J. Liang, C.C. Lin, Y.C. Chiang, H.C. Lee, H.H. Ko, and C.W. Lee. Curcumin nanoparticles ameliorate ICAM-1 expression in TNF-a-treated lung epithelial cells through p47phox and MAPKs/AP-1 pathways. Plos One, 8: e63845, 2013, May. Multidisciplinary Sciences, 8/56=14029%, IF= 3.234.

52. Lo, H.M., C.L. Chen, C.M. Yang, P.H. Wu, C.J. Tsou, K.W. Chiang and W.B. Wu. The carotenoid lutein enhances matrix metalloproteinase-9 production and phagocytosis through intracellular ROS generation and ERK1/2, p38 MAPK, and RARβ activation in murine macrophages. J. Leukoc. Biol. 93: 723–735; 2013, May. HEMATOLOGY, 13/68=19.12%, IF=4.189.

53. Hsieh, H.L., C.C. Lin, L.D. Hsiao and C.M. Yang.* High glucose induces reactive oxygen species-dependent matrix metalloproteinase-9 expression and cell migration in brain astrocytes. Mol. Neurobiol. 48:601-614; 2013, Dec. Neuroscience, 36/252=14.29%, IF=5.137.  

54. Lin, C.C., I.T. Lee, W.B. Wu, C.J. Liu, H.L. Hsieh, Li-Der Hsiao, Chien-Chung Yang, and C.M. Yang.* Thrombin mediates migration of rat brain astrocytes via PLC, Ca2+, CaMKII, PKCa, and AP-1-dependent matrix metalloproteinase-9 expression. Mol. Neurobiol. 48:616-630, 2013, Dec. Neuroscience, 36/252=14.29%, IF=5.137.

55. Lee, I.T., C.C. Lin, W.N. Lin, W.L. Wu, L.D. Hsiao and C.M. Yang.* Lung inflammation caused by adenosine-5'-triphosphate is mediated via Ca2+/PKCs-dependent COX-2/PGE2 induction. International J. Biochem. Cell Biol. 45:1657-1668, 2013, Aug. Cell Biology, 68/184=36.96%, IF=4.046.

56. Yang C.M.,* I.T. Lee, R.C. Hsu, H.L. Hsieh, H.C. Tseng, P.L. Chi, and L.D. Hsiao. NADPH oxidase/ROS-dependent PYK2 activation is involved in TNF-a-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells. Toxicol. Appl. Pharmacol. 272: 431-442, 2013, Oct. Toxicology, 13/87=14.94%, IF=3.705.

57. Lee, I.T., C.C. Lin, S.E. Cheng, L.D. Hsiao, Y.C. Hsiao, and C.M. Yang.* TNF-a induces cytosolic phospholipase A2 expression in human lung epithelial cells via JNK1/2- and p38 MAPK-dependent AP-1 activation. Plos One, 8(9):e72783. 2013, Sep. Multidisciplinary Sciences, 8/56=14029%, IF= 3.234.

58. Lee, I.T. and C.M. Yang.* Inflammatory signalings involved in airway and pulmonary diseases. Mediators of Inflammation. 791231, 2013, Apr. (Review paper). Immunology, 58/148=39.19%, IF= 3.236.

59. Hsieh, H.L. and C.M. Yang.* Role of redox signaling in neuroinflammation and neurodegenerative diseases. BioMed Research International. 484613, 2013, Dec.

60. Lin, C.C., I.T. Lee, P.L. Chi, H.L. Hsieh, S.E. Cheng, L.D. Hsiao, C.J. Liu, and C.M. Yang.* c-Src/Jak2/PDGFR/PKCd-dependent MMP-9 induction is required for thrombin-stimulated rat brain astrocytes migration. Mol. Neurobiol. 49:658-672, 2014, Apr. Neuroscience, 36/252=14.29%, IF=5.137.

61. Lin, C.C., H.L. Hsieh, P.L. Chi, C.C. Yang, L.D. Hsiao, and C.M. Yang.* Up-regulation of COX-2/PGE2 by ET-1 mediated through Ca2+-dependent signals in mouse brain microvascular endothelial cells. Mol. Neurobiol. 49:1256-1269, 2014, Jun. Neuroscience, 36/252=14.29%, IF=5.137.

62. Chi P.L., C.J. Liu, I.T. Lee, Y.W. Chen, L.D. Hsiao and C.M. Yang.* HO-1 induction attenuates TNF-a-induced cytosolic phospholipase A2 expression via inhibition of PKCa-dependent NADPH oxidase/ROS and NF-kB cascade. Mediators of Inflammation. 279171, 2014, Jan. Immunology, 58/148=39.19%, IF= 3.236. 

63. Tsai, C.L., W.C. Chen, I.T. Lee, S.E. Cheng, and C.M. Yang.* c-Src-dependent transactivation of PDGFR contributes to TNF-a-induced MMP-9 expression and functional impairment in osteoblast-like MC3T3-E1 cells. Bone. 60: 186-197, 2014, Mar. ENDOCRINOLOGY & METABOLISM, 38/128=29.67%, IF=3.973.

64. Hsieh, H.L., P.L. Chi, C.C. Lin, C.C. Yang, and C.M. Yang.* Up-regulation of ROS-dependent matrix metalloproteinase-9 from high glucose-challenged astrocytes contributes to the neuronal apoptosis. Mol. Neurobiol. 50(2):520-33, 2014, Oct. Neuroscience, 36/252=14.29%, IF=5.137.

65. Yang, C.M.*, I.T. Lee, P.L. Chi, S.E. Cheng, L.D. Hsiao, and C.K. Hsu. TNF-a induces cytosolic phospholipase A2 expression via Jak2/PDGFR-dependent Elk-1/p300 activation in human lung epithelial cells. Am. J. Physiol. Lung Mol. Cell. Biol., 306 (6): L543-L551, 2014, Mar. Physiology, 14/83=16.87%, IF=4.080. 

66. Chi, P.L., Y.C. Chuang, Y.W. Chen, C.C. Lin, and C.M. Yang.* The CO donor CORM-2 inhibits LPS-induced vascular cell adhesion molecule-1 expression and leukocyte adhesion in human rheumatoid synovial fibroblasts. Br. J. Pharmacol., 171(12):2993-3009, 2014, Jun. Pharmacology, 24/254=9.45%, IF=4.842.

67. Hsu C.K., I.T. Lee, C.C. Lin, L.D. Hsiao, and C.M. Yang.* Nox2/ROS-dependent human antigen R translocation contributes to TNF-a-induced SOCS-3 expression in human tracheal smooth muscle cells. Am. J. Physiol. Lung Mol. Cell. Biol., 306 (6): L521-L533, 2014, Mar. Physiology, 14/83=16.87%, IF=4.080.

68. Tsai, C.L., H.L. Hsieh, P.L. Chi, W.C. Chen, L.D. Hsiao, and C.M. Yang.* TNF-a induces MMP-9 expression and soluble ICAM-1 release via TRAF2, c-Src, MAPKs and NF-kB in osteoblast-like MC3T3-E1 cells. J. Biomed. Sci. 21(1):12, 2014, Feb. MEDICINE, RESEARCH & EXPERIMENTAL, 50/123=40.65%, IF= 2.763.

69. Cheng, S.E., I.T. Lee, C.C. Lin, and C.M. Yang.* Thrombin induces ICAM-1 expression in human lung epithelial cells via c-Src/PDGFR/PI3K/Akt-dependent NF-kB/p300 activation. Clin. Sci., 127(3):171-183, 2014, Aug. MEDICINE, RESEARCH & EXPERIMENTAL, 13/123=10.57%, IF=5.598.

70. Lee IT, Lin CC, Hsu CK, Wu MY, Cho RL, and Yang CM. * Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung epithelial cells. Clin. Sci., 127(6):375-390, 2014, Sep. MEDICINE, RESEARCH & EXPERIMENTAL, 13/123=10.57%, IF=5.598.

71. Chien, T.Y., H.L. Hsieh, P.L. Chi, and C.M. Yang.* PAR-1-dependent COX-2/PGE2 production contributes to cell proliferation via EP2 in primary human cardiomyocytes. Br. J. Pharmacol. 171(19):4504-19, 2014, Oct. Pharmacology, 24/254=9.45%, IF=4.842.

72. Hsu C.K., I.T. Lee, C.C. Lin, L.D. Hsiao, and C.M. Yang.* Sphingosine-1-phosphate mediates COX-2 expression and PGE2/IL-6 secretion via c-Src-dependent AP-1 activation. J. Cell. Physiol., 230(3):702-15, 2015, Mar. Physiology, 15/83=18.07%, IF=3.839.

73. Lee, I.T., H.W. Liu, P.L. Chi,  C.C. Lin, L.D. Hsiao, and C.M. Yang.* TNF-a mediates PKCd/JNK1/2/c-Jun-dependent monocyte adhesion via ICAM-1 induction in human retinal pigment epithelial cells. Plos One, 10(2):e0117911. 2015, Feb. Multidisciplinary Sciences, 8/56=14.29%, IF= 3.234.

74. Lin, C.C., I.T. Lee, C.H. Hsu, P.L. Chi, L.D. Hsiao, and C.M. Yang.* Sphingosine-1-phosphate mediates ICAM-1 expression and monocyte adhesion via p38 MAPK and p42/p44 MAPK-dependent Akt activation. Plos ONE, 10(3):e0118473, 2015, Mar. Multidisciplinary Sciences, 8/56=14029%, IF= 3.234.

75. Lin, C.C., H.L. Hsieh, H.W. Liu, L.D. Hsiao, and C.M. Yang.* BK induces cPLA2 expression via an autocrine loop involving COX-2-derived PGE2 in rat brain astrocytes. Mol. Neurobiol., 51:1103–1115, 2015, Jun. Neuroscience, 36/252=14.29%, IF=5.137.

76. Yang, C.M.*, H.L. Hsieh, P.H. Yu, C.C. Lin, and S.W. Liu. IL-1b induces MMP-9-dependent brain astrocytic migration via transactivation of PDGF receptor/NADPH oxidase 2-derived reactive oxygen species signals. Mol. Neurobiol., 52(1):303–317, 2015, Aug. Neuroscience, 36/252=14.29%, IF=5.137.

77. Chi, P.L., C.C. Lin, Y.W. Chen, L.D. Hsiao, and C.M. Yang.* CO induces Nrf2-dependent heme oxygenase-1 transcription by cooperating with Sp1 and c-Jun in rat brain astrocytes. Mol. Neurobiol., 52(1):277–292, 2015, Aug. Neuroscience, 36/252=14.29%, IF=5.137.

78. Yang, C.M.*, I.T. Lee, C.C. Lin, Y.C. Tai, C.K. Hsu, H.L. Hsieh, P.L. Chi, and L.D. Hsiao. c-Src-dependent transactivation of EGFR mediates CORM-2-induced HO-1 expression in human tracheal smooth muscle cells. J. Cell. Physiol., 230(10):2351-2361, 2015, Oct. Physiology, 15/83=18.07%, IF=3.839.

79. Chien, P.T., C.C. Lin, L.D. Hsiao, and C.M. Yang.* c-Src/Pyk2/EGFR/PI3K/Akt/CREB-activated pathway contributes to human cardiomyocyte hypertrophy:role of COX-2 induction. Mol Cell Endocrinol. 409: 59–72, 2015, Jul. Endocrinology & Metabolism, 30/128=23.44%, IF=4.4051.

80. Lin, C.C., W.N. Lin, W.C. Hou, L.D. Hsiao, and C.M. Yang.* Endothelin-1 induces VCAM-1 expression-mediated inflammation via receptor t yrosine kinases and Elk/p300 in human tracheal smooth muscle cells. Am. J. Physiol. Lung Mol. Cell. Biol., 309(3):L211-L225. 2015, Aug. Physiology, 14/83=16.87%, IF=4.080.  

81. Lin, C.C., C.S. Pan, C.Y. Wang, S.W. Liu, L.D. Hsiao, and C.M. Yang.* Tumor necrosis factor-a induces VCAM-1-mediated inflammation via c-Src-dependent transactivation of EGF receptors in human cardiac fibroblasts. J. Biomed. Sci., 2015, 22:53-67, Jul. MEDICINE, RESEARCH & EXPERIMENTAL, 50/123=40.65%, IF= 2.763.

82. Hsu C.K., C.C. Lin, I.T. Lee, L.D. Hsiao, and C.M. Yang.* Mevastatin ameliorates sphingosine-1-phosphate-induced COX-2/PGE2-dependent cell migration via FoxO1 and CREB translocation. Br. J. Pharmacol. 172(22):5360-76, 2015, Nov. Pharmacology, 24/254=9.45%, IF=4.842.

83. Chien, P.T., C.C. Lin, L.D. Hsiao, and C.M. Yang.* Induction of HO-1 by carbon monoxide releasing molecule-2 attenuates thrombin-induced COX-2 expression and hypertrophy in primary human cardiomyocytes. Toxicol. Appl. Pharmacol. Toxicol. Appl. Pharmacol. 289: 349-359, 2015, Dec. Toxicology, 13/87=14.94%, IF=3.705.

84. Yang, C.C., C.C. Lin, P.T. Chien, L.D. Hsiao, and C.M. Yang.* Thrombin/matrix metalloproteinase-9-dependent SK-N-SH cell migration is mediated through a PLC/PKC/MAPKs/NF-kB cascade. Mol. Neurobiol., 2016, in press. Neuroscience, 36/252=14.29%, IF=5.137.

 

 
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