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| Title: | Lipopolysaccharide induces cellular hypertrophy through calcineurin/NFAT-3 signaling pathway in H9c2 myocardiac cells |
| Authors: | Chung-Jung Liu;Yi-Chang Cheng;Kung-Wei Lee;Hsi-Hsien Hsu;Chun-Hsien Chu;Fuu-Jen Tsai;Chia-Yih Chu;Jer-Yuh Liu;Wei-Wen Kuo;Chih-Yang Huang |
| Date: | 2008-06 |
| Issue Date: | 2009-12-23 06:21:57 (UTC+0) |
| Publisher: | Asia University |
| Abstract: | Evidences suggest that lipopolysaccharide (LPS) participates in the inflammatory response in the cardiovascular system; however, it is unknown if LPS is sufficient to cause the cardiac hypertrophy. In the present study, we treated H9c2 myocardiac cells with LPS to explore whether LPS causes cardiac hypertrophy, and to identify the precise molecular and cellular mechanisms behind hypertrophic responses. Here we show that LPS challenge induces pathological hypertrophic responses such as the increase in cell size, the reorganization of actin filaments, and the upregulation of hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in H9c2 cells. LPS treatment significantly promotes the activation of GATA-4 and the nuclear translocation of NFAT-3, which act as transcription factors mediating the development of cardiac hypertrophy. After administration of inhibitors including U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin inhibitor), FK506 (calcineurin inhibitor), and QNZ (NFκB inhibitor), LPS-induced hypertrophic characteristic features, such as increases in cell size, actin fibers, and levels of ANP and BNP, and the nuclear localization of NFAT-3 are markedly inhibited only by calcineurin inhibitors, CsA and FK506. Collectively, these results suggest that LPS leads to myocardiac hypertrophy through calcineurin/NFAT-3 signaling pathway in H9c2 cells. Our findings further provide a link between the LPS-induced inflammatory response and the calcineurin/NFAT-3 signaling pathway that mediates the development of cardiac hypertrophy. |
| Relation: | MOLECULAR AND CELLULAR BIOCHEMISTRY 313 (1-2): 167-178 |
| Appears in Collections: | [醫學暨健康學院] 期刊論文
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