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楊春茂

老師姓名: 楊春茂 (Chuen-Mao Yang)

照片:

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.tw

個人網頁網址

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研究室現況:

博士後研究員 0

博士班研究生 2

碩士班研究生 3

專任研究助理 2

大學部專題生 0

 

 

研究方向及研究室特色:

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、BKoxLDLIL-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-2cPLA2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-9COX-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.

     

 

    Proposed mechanisms of pro-inflammatory factors-stimulated activation of various signaling molecules and transcription factors leading to expression of MMP-9 in brain astrocytes. 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. CaMKII, calmodulin kinase II; PDGFR, platelet-derived growth factor receptor; PI3K, phosphoinositide-3’-kinase; MAPKs, mitogen activated protein kinases; NF-kB, PKCs, protein kinase Cs; Nox, NADPH oxidase; ROS, reactive oxygen species; Nuclear factor-kB; AP-1, activator protein-1.

 

2. 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.

 

      

3. 發炎標的蛋白的表現與心血管疾病的關係:

目前心血管疾病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-LDL、細胞激素及Sphigosine 1-phosphat可以造成慢性血管內皮的損傷、血管內膜平滑肌細胞與心肌細胞的增生,與誘發各種發炎標的蛋白cPLA2COX-2VCAM-1ICAM-1MMP-9的表現,這些現象可能在心血管疾病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 MAPKAP-1NF-kB等訊號分子調控發炎基因cPLA2COX-2VCAM-1ICAM-1MMP-9的表現。

 

 

最近五年所發表論文著作及專利:

1. 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, 15/81=18.51%, IF=4.414.

2. 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, 44/261=16.86%, IF=5.076.

3. 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,    46/190=24.21%, IF=5.324.

4. 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, 36/261=13.79%, IF=4.235.

5. 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, 36/261=13.79%, IF=4.235.

6. 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, 15/64=23.44%, IF= 2.766.

7. 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, 15/64=23.44%, IF= 2.766.

8. 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, 18/71=25.35%, IF=4.224.

9. 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, 44/261=16.86%, IF=5.076.

10.  Lin, C.C., I.T. Lee, W.B. Wu, C.J. Liu, H.L. Hsieh, L.D. Hsiao, C.C. 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, 44/261=16.86%, IF=5.076.

11. 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, 88/190 =46.81%, IF=3.505.

12. 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, 19/94=20.21%, IF=3.616.

13. Lee, I.T. and C.M. Yang.* Inflammatory signalings involved in airway and pulmonary diseases. Mediators of Inflammation. 791231, 2013, Apr. (Review paper). Immunology, 61/155=39.35%, IF= 3.549.

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

15. 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, 44/261=16.86%, IF=5.076.

16. 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, 44/261=16.86%, IF=5.076.

17. 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, 61/155=39.35%, IF= 3.549.

18. 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, 28/143=19.58%, IF=4.455.

19. 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, 44/261=16.86%, IF=5.076.

20. 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, 11/83=13.25%, IF=4.092.

21. 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 & Pharmacy, 12/261=4.6%, IF=6.81.

22. 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, 11/83=13.25%, IF=4.092.

23. 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, 46/133=34.59%, IF=3.466.

24. 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, 17/133=12.78%, IF=5.22.

25. 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, 17/133=12.78%, IF=5.22.

26. 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 & Pharmacy, 12/261=4.6%, IF=6.81.

27. 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, 15/64=23.44%, IF= 2.766.

28. 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, 13/83=15.66%, IF=3.923.

29. 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, 15/64=23.44%, IF= 2.766.

30. 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, 44/261=16.86%, IF=5.076.

31. 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, 44/261=16.86%, IF=5.076.

32. 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, 44/261=16.86%, IF=5.076.

33. 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, 13/83=15.66%, IF=3.923.

34. 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, 50/143=35%, IF=3.563.

35. 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 tyrosine kinases and Elk/p300 in human tracheal smooth muscle cells. Am. J. Physiol. Lung Mol. Cell. Biol., 309(3):L211-L225. 2015, Aug. Physiology, 11/83=13.25%, IF=4.092.  

36. 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, 46/133=34.59%, IF=3.466.

37. 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. 289:349-359, 2015, Dec. Toxicology, 19/94=20.21%, IF=3.616.

38. 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. 172:5360-5376, 2015, Oct. Pharmacology & Pharmacy, 12/261=4.6%, IF=6.81.

39. Shih, R.H., C.Y. Wang, and C.M. Yang.* NF-kB signaling pathways in Neurological inflammation: A mini review. Front. Mol. Neurosci., 8:77, 2015, Dec. Neuroscience, 74/261=28.35%, IF=3.902.

40. 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., 53(9): 5833-5846, 2016, Nov. Neuroscience, 44/261=16.86%, IF=5.076.

41. Cho, R.L., C.C. Yang, C.C. Lin, I.T. Lee, S.E. Cheng, P.L. Chi, L.D. Hsiao, and C.M. Yang.* Lipopolysaccharide induces ICAM-1 expression through a c-Src/NADPH oxidase/ROS/p42/p44 MAPK-dependent NF-kB pathway in human pulmonary alveolar epithelial cells. Am. J. Physiol. Lung Mol. Cell. Biol., 310(7):L639-57, 2016, Apr. Physiology, 11/83=13.25%, IF=4.092.

42. Lin, C.C., Yang, C.C., C.Y. Wang, H.C. Tseng, C.S. Pan, L.D. Hsiao and C.M. Yang.* NADPH oxidase/ROS-dependent VCAM-1 induction on TNF-α-challenged human cardiac fibroblasts enhances monocyte adhesion. Front. Pharmacol. 6:310, 2016, Jan. Pharmacology & Pharmacy, 48/261=18.39%, IF=3.831.

43. Lin, C.C., C.C. Yang, R.L. Cho, C.Y. Wang, L.D. Hsiao and C.M. Yang.* Sphingosine 1-phosphate-induced ICAM-1 expression via NADPH oxidase/ROS-dependent NF-kB cascade on human pulmonary alveolar epithelial cells. Front. Pharmacol. 7:80, 2016, Mar. Pharmacology & Pharmacy, 48/261=18.39%, IF=3.831.

44. Yang, C.M., S.H. Yang, T.H. Lee, J.Y. Fang, M.J. Jou and H.L. Hsieh. Evaluation of anti-inflammatory effects of Helminthostachys zeylanica extracts via inhibiting Bradykinin-

induced MMP-9 expression in brain astrocytes. Mol. Neurobiol., 53(9): 6006, 2016. Nov. Neuroscience, 44/261=16.86%, IF=5.076.

45. Chen, H.M., Yang, C.M., Chang, J.F., Wu, C.S., Sia. K.C, and  Lin W.N. AdipoR-increased intracellular ROS promoted cPLA2 and COX-2 expression via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells. Am. J. Physiol. Lung Mol. Cell. Biol., 311(2):L255-269, 2016, Jun. Physiology, 11/83=13.25%, IF=4.092. 

46. Lin, H.R., Wu, Y.H., Yen, W.C., Yang, C.M, and Chiu, D.T. Diminished COX-2/PGE2-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells. Plos ONE, 11(4):e0153462, 2016,   Multidisciplinary Sciences, 15/64=23.44%, IF= 2.766.

47. Lin, C.C., W.N. Lin, R.L. Cho  , C.Y. Wang, L.D. Hsiao and C.M. Yang.* TNF-a-induced cPLA2 expression via NADPH oxidase/reactive oxygen species-dependent NF-kB cascade on human pulmonary alveolar epithelial cells. Front. Pharmacol. 7:447, 2016, Nov. Pharmacology & Pharmacy, 48/261=18.39%, IF=3.831.

48. Yang, C.M., C.C. Lin, and H.L. Hsieh. High glucose-derived oxidative stress-dependent heme oxygenase-1 expression from astrocytes contributes to the neuronal apoptosis. Mol. Neurobiol., 54(1): 470-483, 2017, Jan. Neuroscience, 44/261=16.86%, IF=5.076.

49. Yang, C.M.*, Y.W. Chen, P.L. Chi, C.C. Lin and L.D. Hsiao. Resveratrol inhibits BK-induced COX-2 transcription by suppressing acetylation of AP-1 and NF-kB in human rheumatoid  arthritis synovial fibroblasts. Biochem. Pharmacol. 132:77-91, 2017. May. Pharmacology & Pharmacy, 36/261=13.79%, IF=4.235.

50. Yang, C.C., Hsiao, L.D., Yang, C.M*, and Lin, C.C. Thrombin Enhanced Matrix Metalloproteinase-9 Expression and Migration of SK-N-SH Cells via PAR-1, c-Src, PYK2, EGFR, Erk1/2 and AP-1. Mol. Neurobiol., 54(5): 3476-3491, 2017. July. Neuroscience, 44/261=16.86%, IF=5.076.

51. Lin, C.C., C.C. Yang., L.D. Hsiao., S.Y. Chen, and C.M. Yang.* Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuronflammation. Front Mol Neurosci. 10: 387, 2017, Nov. Neuroscience, 74/261=28.35%, IF=3.902.

52. Lin, C.C., Chiang, Y.C., Cho, R.L., Lin, W. N., Yang, C.C., Hsiao, L.D, and C.M. Yang.* Up-regulation of PYK2/PKCα-dependent HO-1 by CO-releasing molecule (CORM)-2 attenuates TNF-α-induced lung inflammation. Br. J. Pharmacol. 175(3): 456-468, 2018, Feb. Pharmacology & Pharmacy, 12/261=4.6%, IF=6.81.

53. Cho, R.L., Lin. W.N., Wang, C.Y., Yang, C.C., Hsiao, L.D., Lin, C.C and Yang, C.M.* Heme oxygenase-1 induction by rosiglitazone via PKCa/AMPKa/p38MAPKa/ SIRT1/

PPARγ pathway suppresses lipopolysaccharide-mediated pulmonary inflammation.  Biochem. Pharmacol. 148:222-237, 2018. Feb. Pharmacology & Pharmacy, 36/261=13.79%, IF=4.235.

54. Lin, C.C., C.C. Yang, Y.W. Chen, L.D. Hsiao, and C.M. Yang.* Arachidonic acid induces

ARE/Nrf2-dependent heme oxygenase-1 transcription in rat brain astrocytes. Mol.    

Neurobiol., 55(4):3328-3343, 2018, Apr. Neuroscience, 44/261=16.86%, IF=5.076.

 

 

獲獎紀錄: (含 校內及校外有關 研究教學輔導等獎項均可)

1. Travel award, American Society of Pharmacology and Experimental

Therapeutics,   1986.

2.國科會優等研究獎: 1992, 1993

3.台灣藥理學會傑出研究獎: 1995

4.長庚大學優良教師研究獎: 2003, 2010

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