ZAK induces MMP-2 activity via JNK/p38 signals and reduces MMP-9 activity by increasing TIMP-1/2 expression in H9c2 cardiomyoblast cells

Yi Chang Cheng, Wei Wen Kuo, Hsi Chin Wu, Tung Yuan Lai, Chun Hsien Wu, Jin Ming Hwang, Wen Hong Wang, Fuu Jen Tsai, Jaw Ji Yang, Chih Yang Huang, Chun Hsien Chu

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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-β1) 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.

Original languageEnglish
Pages (from-to)69-77
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume325
Issue number1-2
DOIs
Publication statusPublished - 2009 Jan 29

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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