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Kowit-Yu Chong

Kowit-Yu Chong

Highest Degree

Ph. D. in Pharmacology, Southern Illinois University, IL, USA

Areas of Specialty

Stem cell therapy, Regenerative medicine, multidrug-resistant cancer cells

Office Phone

+886-3-2118800 x 3332;

+886-3-2118393

Lab phone

+886-3-2118800 x 3433

Research website:

Regenerative Medicine Laboratory

E-mail

kchong@mail.cgu.edu.tw

Lab & Research Interest

1. Investigation of the protective effects of hypoxia preconditioned mesenchymal stem cells against Bleomycin-induced Pulmonary Fibrosis in mouse model.

      Pulmonary fibrosis is a progressive diffuse parenchymal lung disorder with unknown etiology. It is characterized by an intricate cytokine network and abnormal deposition of mesenchymal cells. Recent studies indicated that nitric oxide production may augment TGF-β1 activity, which is proven to be a strong stimulator of collagen, fibronectin, and proteoglycan synthesis. Furthermore, several studies indicated that gene therapy with overexpressed hepatocyte growth factor (HGF) has protective effect against lung damage, and preventing subsequent fibrogenesis of bleomycin-induced fibrosis animal model. Moreover, several studies demonstrated that mesenchymal stem cells (MSCs) have significantly reduced damage in the alveoli and were engrafted at injury sites as well as were a better gene delivery cargo. Despite of its success, it has also been demonstrated that amount of engrafted MSCs decreased dramatically after 24 hr transplantation due to exposed to the oxidative microenvironment. In additions, hypoxia preconditioned-MSCs have protected hypoxic cells against oxidative stress and enhanced recovery of myocardial function in infarcted heart. Taken together, to improve the survival of the transplanted MSCs, we proposed to design utilization of hypoxia preconditioned-MSCs for prolong the survival rate upon engraftment and enhance the therapeutic effects. This study should improve our understanding of the protective effects of hypoxia preconditioned-stem cell therapy approaches. Furthermore, this novel approach may lead a new avenue of therapy for pulmonary fibrosis.

2. Investigation of the Relationship between Drug Resistance and Wnt pathway in Multiple Drug Resistant Cancer Cell line

      Multiple drug resistance (MDR) is a major obstacle to attenuating the effectiveness of chemotherapy to many human malignancies. Proteasome inhibition induces apoptosis in a variety of cancer cells and is recognized as a novel anticancer therapy approach. Despite its success, some multiple myeloma patients are resistant or become refractory to ongoing treatment by bortezomib suggesting that chemoresistant cancer cells may have developed a novel mechanism directed against the proteasome inhibitor. The present study aimed to investigate potential mechanism(s) of attenuation in a MDR cell line, MES-SA/Dx5. We found that compared to the parental human uterus sarcoma cell line MES-SA cells, MES-SA/Dx5 cells highly expressed the ABCB1 was more resistant to MG132 and bortezomib, escaping the proteasome inhibitor-induced apoptosis pathway. The resistance was reversed by co-treatment of MG132 and the ABCB1 inhibitor verapamil. The data indicated that ABCB1 might play a role in the efflux of MG132 from the MES-SA/Dx5 cells to reduce MG132-induced apoptosis. Furthermore, the canonical Wnt pathway was found activated only in the MES-SA/Dx5 cells through active β-catenin and related transactivation activities. Western blot analysis demonstrated that Wnt-targeting genes, including c-Myc and cyclin D1, were upregulated and were relevant in inhibiting the expression of p21 in MES-SA/Dx5 cells. On the other hand, MES-SA cells expressed high levels of p21 and downregulated cyclin D1 and caused cell cycle arrest. Together, our study demonstrated the existence and participation of ABCB1 and the Wnt pathway in an MDR cell line that attenuated proteasome inhibitor-induced apoptosis.

Publication

  1. Tseng WL, Huang CL, Chong KY, Liao CH, Stern A, Cheng JC, Tseng CP. Reelin is a platelet protein and functions as a positive regulator of platelet spreading on fibrinogen. Cell Mol Life Sci. 67: 641-653, 2010.
  2. Huang CL, Cheng JC, Kitajima K, Nakano T, Yeh CF, Chong KY*, Tseng CP*. Disabled-2 is required for mesoderm differentiation of murine embryonic stem cells. J Cell Physiol225: 92-105, 2010. *Co -Correspondence author.
  3. Tsai TC, Lin W, Yang SH, Cheng WT, Cheng EH, Lee MS, Chong KY, Chen CM. Granzyme G is expressed in the two-cell stage mouse embryo and is required for the maternal-zygotic transition. BMC Dev Biol. 2011: 238208, 2011.
  4. Hung CM, Chen, HL, Chong KY, Chia-Chou Yeh CC, Kao ST, Yeh HM Lin MS, and Chen CM. Gingyo-San Enhances Immunity and Assists Infectious Bursal Disease Vaccination. Evidence-based Compl. and Alt. Medicine 2011: 238208, 2011.
  5. Chong KY, Lai CC, Su CY. Inducible and Constitutive HSP70s confer a synergistic resistance against oxidative insults. Biochem Biophys Res Commun. 430: 774-779, 2013.
  6. Huang TT, Chong KY, Ojcius DM, Wu YH, Ko YF, Wu CY, Martel J, Lu CC, Lai HC, Young JD. Hirsutella sinensis mycelium suppresses interleukin-1β and interleukin-18 secretion by inhibiting both canonical and non-canonical inflammasomes. Sci Rep 3: 1374. 2013.
  7. Chen W, Chen JY, Tung YT, Chen HL, Kuo CW, Chuang CH, Chong KY, Mao FC, Chen CM. High-frequency ultrasound imaging to evaluate liver fibrosis progression in rats and yi guan jian herbal therapeutic effects. Evid Based Complement Alternat Med. 2013: 302325, 2013.
  8. Huang TT, Lai HC, Chen YB, Chen LG, Wu YH, Ko YF, Lu CC, Chang CJ, Wu CY, Martel J, Ojcius DM, Chong KY, Young JD. Cis-resveratrol suppresses IL-1β secretion by inhibiting the non-canonical inflammasome pathway in macrophages. Innate Immun. 20: 735-50, 2014.
  9. Tung YT, Tang TY, Chen HL, Yang SH, Chong KY, and Chen CM. Lactoferrin protects against chemical-induced rat liver fibrosis through inhibiting stellate cells activation. J. Dairy Sci. 97: 3281-91, 2014.
  10. Hung TH, Chen CM, Tseng CP, Shen CJ, Wang HL, Choo KB, Chong KY. FZD1 activates protein kinase C delta-mediated drug-resistance in multidrug-resistant MES-SA/Dx5 cancer cells. Int J Biochem Cell Biol. 53: 55-65, 2014.
  11. Lai CW, Chen HL, Lin KY, Liu FC, Chong KY, Cheng WT, Chen CM. FTSJ2, a heat shock-inducible mitochondrial protein, suppresses cell invasion and migration. PLoS One. 9: e90818, 2014.
  12. Hung TH, Hsu SC, Cheng CY, Choo KB, Tseng CP, Chen TC, Lan YW, Huang TT, Lai HC, Chen CM, Chong KY. Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/β-catenin pathway. Oncotarget. 5: 12273-90, 2014.
  13. Huang TT, Wu SP, Chong KY, Ojcius DM, Ko YF, Wu YH, Wu CY, Lu CC, Martel J, Young JD, Lai HC. The medicinal fungus Antrodia cinnamomea suppresses inflammation by inhibiting the NLRP3 inflammasome. J Ethnopharmacol.155: 154-64, 2014.
  14. Tsai TC, Tung YT, Kuo YH, Liao JW, Tsai HC, Chong KY, Chen HL, Chen CM. Anti-inflammatory effects of Antrodia camphorata, a herbal medicine, in a mouse skin ischemia model. J Ethnopharmacol. 159: 113-21, 2015.
  15. Chong KY, Hsu CJ, Hung TH, Hu HS, Huang TT, Wang TH, Wang C, Chen CM, Choo KB, Tseng CP. Wnt pathway activation and ABCB1 expression account for attenuation of  Proteasome Inhibitor-mediated apoptosis in multidrug-resistant cancer cells. Cancer Biol Ther. 16:149-159, 2015.
  16. Tung YT, Huang PW, Chou YC, lai CW, Wang HP, Ho HC, Yen CC, Tu CY, Tsai TC, Yeh DC, Wang JL, Chong KY, Chen CM. Lung tumorigenesis induced by human vascular endothelial growth factor (hVEGF)-A165 overexpression in transgenic mice and amelioration of tumor.  Oncotarget 6(12), 10222-38, 2015.
  17. Lin MH, Shu JC, Lin LP, Chong KY, Cheng YW, Du JF, Liu ST.Elucidating the Crucial Role of Poly N-Acetylglucosamine from Staphylococcus aureus in Cellular Adhesion and Pathogenesis. PLoS One. 10:e0124216, 2015.
  18. Lan YW, Choo KB, Chen CM, Hung TH, Chen YB, Hsieh CH, Kuo HP, Chong KY#.Hypoxia-Preconditioned Mesenchymal Stem Cells Attenuates Bleomycin-Induced Pulmonary Fibrosis.Stem Cell Res Ther. 6:97, 2015.
  19. Hung TH, Li YH, Tseng CP. Lan YW, Hsu SC, Chen YH, Huang TT, Lai HC, Chen CM, Choo KB, Chong KY#.Knockdown of c-MET induced Apoptosis in ABCB1-Overexpressed Multidrug-Resistance Cancer Cell Lines. Cancer Gene Ther. 22:262-270,2015.
  20. Chen YB, Lan YW, Hung TH, Chen LG, Choo KB, Cheng WT, Lee HS, Chong KY#. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model. Cell Stress Chaperones. 20:643-652,2015.
  21. Chen YB, Lan YW, Chen LG, Huang TT, Choo KB, Cheng WTK, Lee HS, Chong KY#. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model. Cell Stress Chaperones. 20(6):979-89, 2015.
  22. Hsu CY, Shu JC, Lin MH, Chong KY, Chen CC, Wen SM, Hsieh YT, Liao WT. High Glucose Concentration Promotes Vancomycin-Enhanced Biofilm Formation of Vancomycin-Non-Susceptible Staphylococcus aureus in Diabetic Mice.  PLoS One. 10(8):e0134852, 2015.
  23. Huang TT, Lai HC, Ko YF, Ojcius DM, Lan YW, Martel J, Young JD, Chong KY#. Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo. Sci Rep. 5:15282. 2015 doi: 10.1038/srep15282.
  24. Chang YW, Hsieh PW, Chang YT, Lu MH, Huang TF, Chong KY, Liao HR, Cheng JC, Tseng CP. Identification of a novel platelet antagonist that binds to CLEC-2 and suppresses podoplanin-induced platelet aggregation and cancer metastasis. Oncotarget. 2015 Oct 30. doi: 10.18632/oncotarget.5811. [Epub ahead of print]
  25. Shih CL, Chong KY, Hsu SC, Chien HJ, Ma CT, Chang JW, Yu CJ, Chiou CC. Development of a magnetic bead-based method for the collection of circulating extracellular vesicles. N Biotechnol. 25;33:116-22. 2016.
  26. Lai CW, Chen HL, Tsai TC, Chu TW, Yang SH, Chong KY, Chen CM.Sexually Dimorphic Expression of eGFP Transgene in the Akr1A1 Locus of Mouse Liver Regulated by Sex Hormone-Related Epigenetic Remodeling. Sci Rep.  6:24023, 2016.
  27. Chen YL, Hwang TL, Yu HP, Fang JY, Chong KY, Chang YW, Chen CY, Yang HW, Chang WY, Hsieh PW.Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury. Sci Rep. 6:34243,2016.
  28. Lan YW, Theng SM, Huang TT, Choo KB, Chen CM, Kuo HP, Chong KY.Oncostatin M-Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary FibrosisThrough Paracrine Effects of the Hepatocyte Growth Factor. Stem Cells Transl Med.  5:1-12,2016.
  29. Chang PY, Huang Y, Hung TY, Chong KY, Chang YS, Chao CC, Chow KN. Spontaneous metastases in immunocompetent mice harboring a primary tumor driven by oncogene latent membrane protein 1 from Epstein-Barr virus. Biomed J.  39:261-271,2016.
  30. Lai CW, Chen HL, Tu MY1, Lin WY, Röhrig T, Yang SH, Lan YW, Chong KY, Chen CM. A novel osteoporosis model with ascorbic acid deficiency in Akr1A1 gene knockout mice. Oncotarget.  8:7357-7369,2017.
  31. Ying-Wei Lan, Si-Min Theng, Tsung-Teng Huang, Kong Bung Choo, Chuan-Mu Chen, Han-Pin Kuo, Kowit-Yu Chong. Oncostatin M Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary Fibrosis Through Paracrine Effects of the Hepatocyte Growth Factor. Stem Cells Translational Medicine. 6:1006-1017,2017.
  32. Yu-Li Chen, Tsong-Long Hwang, Jia-You Fang, Yu-Hsuan Lan, Kowit-Yu Chong, Pei-Wen Hsieh. Polysaccharides from Kochia scoparia fruits protect mice from lipopolysaccharide-mediated acute lung injury by inhibiting neutrophil elastase. J. Funct. Food. 378: 582-590,2017.
  33. Yu-Tang Tung, Hsiao-Ling Chen, Hsin-Shan Wu, Mei-Hsuan Ho, Kowit-Yu Chong, Chuan-Mu Chen. Kefir Peptides Prevent Hyperlipidemia and Obesity in High-Fat-Diet-Induced Obese Rats via Lipid Metabolism Modulation. Mol Nutr Food Res. 62:1700505,2017.
  34. Yao-Wen Chang, Ching-Ping Tseng, Chih-Hsun Lee, Tsong-Long Hwang, Yu-Li Chen, Mei-Tzu Su, Kowit-Yu Chong, Ying-Wei Lan, Chin-Chung Wu, Kung-Ju Chen, Fen-Hua Lu, Hsiang-Ruei Liao, Chuen Hsueh, and Pei-Wen Hsieh. β-Nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the inhibition of neutrophil-platelet interactions and NET release. Am J Physiol Lung Cell Mol Physiol. 314:L654-669,2018.
  35. Huang TT, Lan YW, Ko YF, Chen CM, Lai HC, Ojcius DM, Martel J, Young JD, Chong KY. Antrodia cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway. J Ethnopharmacol.  28:239-249,2018.