Lipopolysaccharide induces cellular hypertrophy through calcineurin/ NFAT-3 signaling pathway in H9c2 myocardiac cells

Chung Jung Liu, Yi Chang Cheng, Kung Wei Lee, Hsi Hsien Hsu, Chun Hsien Chu, Fuu Jen Tsai, Chang Hai Tsai, Chia Yih Chu, Jer Yuh Liu, Wei Wen Kuo, Chih Yang Huang

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)167-178
Number of pages12
JournalMolecular and Cellular Biochemistry
Volume313
Issue number1-2
DOIs
Publication statusPublished - 2008 Jun 1

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Calcineurin
Hypertrophy
Lipopolysaccharides
Cardiomegaly
Brain Natriuretic Peptide
Atrial Natriuretic Factor
Tacrolimus
Cell Size
Actins
Cardiovascular system
p38 Mitogen-Activated Protein Kinases
Cardiovascular System
Actin Cytoskeleton
Transcription Factors
Up-Regulation
Chemical activation
Fibers

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Liu, Chung Jung ; Cheng, Yi Chang ; Lee, Kung Wei ; Hsu, Hsi Hsien ; Chu, Chun Hsien ; Tsai, Fuu Jen ; Tsai, Chang Hai ; Chu, Chia Yih ; Liu, Jer Yuh ; Kuo, Wei Wen ; Huang, Chih Yang. / Lipopolysaccharide induces cellular hypertrophy through calcineurin/ NFAT-3 signaling pathway in H9c2 myocardiac cells. In: Molecular and Cellular Biochemistry. 2008 ; Vol. 313, No. 1-2. pp. 167-178.
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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.",
author = "Liu, {Chung Jung} and Cheng, {Yi Chang} and Lee, {Kung Wei} and Hsu, {Hsi Hsien} and Chu, {Chun Hsien} and Tsai, {Fuu Jen} and Tsai, {Chang Hai} and Chu, {Chia Yih} and Liu, {Jer Yuh} and Kuo, {Wei Wen} and Huang, {Chih Yang}",
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Liu, CJ, Cheng, YC, Lee, KW, Hsu, HH, Chu, CH, Tsai, FJ, Tsai, CH, Chu, CY, Liu, JY, Kuo, WW & Huang, CY 2008, 'Lipopolysaccharide induces cellular hypertrophy through calcineurin/ NFAT-3 signaling pathway in H9c2 myocardiac cells', Molecular and Cellular Biochemistry, vol. 313, no. 1-2, pp. 167-178. https://doi.org/10.1007/s11010-008-9754-0

Lipopolysaccharide induces cellular hypertrophy through calcineurin/ NFAT-3 signaling pathway in H9c2 myocardiac cells. / Liu, Chung Jung; Cheng, Yi Chang; Lee, Kung Wei; Hsu, Hsi Hsien; Chu, Chun Hsien; Tsai, Fuu Jen; Tsai, Chang Hai; Chu, Chia Yih; Liu, Jer Yuh; Kuo, Wei Wen; Huang, Chih Yang.

In: Molecular and Cellular Biochemistry, Vol. 313, No. 1-2, 01.06.2008, p. 167-178.

Research output: Contribution to journalArticle

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T1 - Lipopolysaccharide induces cellular hypertrophy through calcineurin/ NFAT-3 signaling pathway in H9c2 myocardiac cells

AU - Liu, Chung Jung

AU - Cheng, Yi Chang

AU - Lee, Kung Wei

AU - Hsu, Hsi Hsien

AU - Chu, Chun Hsien

AU - Tsai, Fuu Jen

AU - Tsai, Chang Hai

AU - Chu, Chia Yih

AU - Liu, Jer Yuh

AU - Kuo, Wei Wen

AU - Huang, Chih Yang

PY - 2008/6/1

Y1 - 2008/6/1

N2 - 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.

AB - 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.

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