Author(s): Cheng, YC (Cheng, Yi-Chang); Kuo, WW (Kuo, Wei-Wen); Wu, HC (Wu, Hsi- Chin); Lai, TY (Lai, Tung-Yuan); Wu, CH (Wu, Chun-Hsien); Hwang, JM (Hwang, Jin-Ming);
Wang, WH (Wang, Wen-Hong); Tsai, FJ (Tsai, Fuu-Jen); Yang, JJ (Yang, Jaw-Ji); Huang, CY (Huang, Chih-Yang); Chu, CH (Chu, Chun-Hsien)
Title: ZAK induces MMP-2 activity via JNK/p38 signals and reduces MMP-9 activity by increasing TIMP-1/2 expression in H9c2 cardiomyoblast cells
Source: MOLECULAR AND CELLULAR BIOCHEMISTRY, 325 (1-2): 69-77 MAY 2009 Language: English
Document Type: Article
Author Keywords: ZAK (mixed lineage protein kinase, Leucine-zipper, and sterile-alpha motif kinase); MMP-2/9; TIMP-1/2 and cardiac fibrosis
KeyWords Plus: N-TERMINAL KINASE; MYOCARDIAL-INFARCTION; HEART-FAILURE;
MATRIX METALLOPROTEINASES; CARDIAC MYOCYTES; HYPERTROPHIC GROWTH;
INHIBITION; P38; PATHWAYS; PROTEIN
Abstract: Leucine-zipper and sterile-alpha motif kinase (ZAK) is the key intra-cellular mediator protein in cardiomyocyte hypertrophy induction by transforming growth factor beta 1 (TGF- beta 1) which has also been identified as a profibrotic cytokine involved in cardiac fibrosis progression. We hypothesized whether ZAK over-expression causes cardiac scar formation due to the extra-cellular matrix (ECM) degraded enzyme regulation in this paper. Using immuno-histochemical analysis of the human cardiovascular tissue array, we found a positively significant association between ZAK over-expression and myocardial scars. ZAK over-expression in H9c2 cardiomyoblast cells increases the metalloproteinase tissue inhibitor 1/2 (TIMP-1/2) protein level, which reduces matria metalloproteinase-9 (MMP-9) activity and also activates c-JNK N-terminal kinase 1/2 (JNK1/2) and p38 signaling, which induces MMP-2, possibly resulting in cardiac fibrosis. Taken together, ZAK activity inhibition may be a good strategy to prevent the cardiac fibrosis progression.
Addresses: [Cheng, Yi-Chang] China Med Univ Hosp, Emergency Dept, Taichung, Taiwan;
[Kuo, Wei-Wen; Wu, Chun-Hsien] China Med Univ, Dept Biol Sci & Technol, Taichung 404, Taiwan; [Wu, Hsi-Chin] China Med Univ Hosp, Sch Med, Taichung, Taiwan; [Lai, Tung-Yuan]
China Med Univ, Postbaccalaureate Sch Chinese Med, Taichung 404, Taiwan; [Hwang, Jin- Ming] Chung Shan Med Univ, Sch Appl Chem, Taichung, Taiwan; [Wang, Wen-Hong]
Taichung Vet Gen Hosp, Dept Nutr, Taichung, Taiwan; [Tsai, Fuu-Jen] China Med Univ, Dept Pediat Med Res & Med Genet, Taichung 404, Taiwan; [Yang, Jaw-Ji] Chung Shan Med Univ, Sch Dent, Taichung, Taiwan; [Huang, Chih-Yang] China Med Univ, Grad Inst Chinese Med Sci, Taichung 404, Taiwan; [Huang, Chih-Yang; Chu, Chun-Hsien] China Med Univ, Grad Inst Basic Med Sci, Taichung 404, Taiwan; [Huang, Chih-Yang] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 413, Taiwan
Reprint Address: Chu, CH, China Med Univ, Grad Inst Basic Med Sci, 91 Hsueh Shih Rd, Taichung 404, Taiwan.
E-mail Address: [email protected]
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Cited Reference Count: 38 Times Cited: 0
Publisher: SPRINGER
Publisher Address: VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
ISSN: 0300-8177
DOI: 10.1007/s11010-008-0021-1
29-char Source Abbrev.: MOL CELL BIOCHEM ISO Source Abbrev.: Mol. Cell. Biochem.
Source Item Page Count: 9 Subject Category: Cell Biology ISI Document Delivery No.: 428HZ
