TGF-β1 induces cardiac hypertrophic responses via PKC-dependent ATF-2 activation

Lim, Joong-Yeon; Park, Sung‐Joon; Hwang, Hayoung; Park, Eun Jung; Nam, Jae Hwan; Kim, Joon; Park, Sang Ick

doi:10.1016/j.yjmcc.2005.06.016

Cited by 89 publications

(64 citation statements)

References 23 publications

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“…13,[16][17][18] TGFb1 alone also stimulated comparable hypertrophic responses to those induced by Ang II treatment (Figures 1a-c), and in a similar way to a previous report. 19 Functional TGFb1 signaling is essential for the stimulation of cardiomyocyte hypertrophy by Ang II Immunoblot experiments showed that TGFb1 and AngII stimulated phosphorylation of Smad2 in PNCM cells (Figure 2a), in a similar way to previous reports. 9,20,21 Inhibition of TGFb1 signaling with 6 mM SB431542 blocked phospho-Smad2 responses to Ang II and TGFb (Figure 2a) indicating that the Smad 2 phosphorylation response to Ang II requires TGFb receptor activity.…”

Section: Ang II and Tgfb1 Induce Similar Hypertrophic Responses In Vitrosupporting

confidence: 88%

Angiotensin II-induced cardiomyocyte hypertrophy in vitro is TAK1-dependent and Smad2/3-independent

et al. 2011

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Cardiac hypertrophy occurs as an adaptation to hypertension but a sustained hypertrophic response can ultimately lead to heart failure. Angiotensin-II (Ang II) is released following hemodynamic overload and stimulates a cardiac hypertrophic response. AngII also increases expression of the regulatory cytokine, transforming growth factor-b1 (TGFb1), which is also implicated in the cardiac hypertrophic response and can stimulate activation of Smad2/3 as well as TGFb-activated kinase 1 (TAK1) signaling mediators. To better understand the downstream signaling events in cardiac hypertrophy, we therefore investigated activation of Smad2/3 and TAK1 signaling pathways in response to Ang II and TGFb1 using primary neonatal rat cardiomyocytes to model cardiac hypertrophic responses. Small interfering RNA (siRNA) knockdown of Smad 2/3 or TAK1 protein or addition of the TGFb type I receptor inhibitor, SB431542, were used to investigate the role of downstream mediators of TGFb signaling in the hypertrophic response. Our data revealed that TGFb1 stimulation leads to cardiomyocyte hypertrophic phenotypes that were indistinguishable from those occurring in response to Ang II. In addition, inhibition of the TGFb1 type receptor abolished Ang II-induced hypertrophic changes. Furthermore, the hypertrophic response was also prevented following siRNA knockdown of TAK1 protein, but was unaffected by knockdown of Smad2/3 proteins. We conclude that Ang II-induced cardiomyocyte hypertrophy in vitro occurs in a TAK1-dependent, but Smad-independent, manner.

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Section: Ang II and Tgfb1 Induce Similar Hypertrophic Responses In Vitrosupporting

confidence: 88%

Angiotensin II-induced cardiomyocyte hypertrophy in vitro is TAK1-dependent and Smad2/3-independent

et al. 2011

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“…CRE-mediated transcription is a convergence point for multiple pathways initiated by differentiation signals. The transcriptional activity of CREB is regulated by phosphorylation at Ser133 in the P-box or KID of the protein; this domain includes several consensus phosphorylation sites for a variety of kinases, such as PKA, CaMKIV, and MAPKs (Lim et al, 2005). Our result demonstrated that CREB was mediated by RA independent of the conventional PKA pathway.…”

Section: Discussionmentioning

confidence: 63%

pCREB is Involved in Neural Induction of Mouse Embryonic Stem Cells by RA

Shan

Shen

et al. 2008

The Anatomical Record

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Mouse embryonic stem (ES) cells can be induced by various chemicals to differentiate into a variety of cell types in vitro. In our study, retinoic acid (RA), one of the most important inducers, used at a concentration of 5 mM, was found to induce the differentiation of ES cells into neural progenitor cells (NPCs). During embryoid body (EB) differentiation, the level of active cyclic AMP response element-binding protein (CREB) was relatively high when 5 mM RA treatment was performed. Inhibition of CREB activity committed EBs to becoming other germ layers, whereas increased expression of CREB enhanced NPC differentiation. Moreover, RA increased the expression of active CREB by enhancing the activity of JNK. Our research suggests that CREB plays a role in RA-induced NPC differentiation by increasing the expression of active JNK. Anat Rec,

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“…In support of this hypothesis, very recent work shows that overexpression of human Tert can downregulate protein kinase C and suppress Ras/Raf/Mek/Erk signaling (Wang et al, 2005a). Of note, TGF-b is well known to activate MAP kinase signaling in numerous cell types (Javelaud and Mauviel, 2005), and there is also some evidence linking activation of protein kinase C to the upregulation of gene expression by TGF-b (Liao et al, 2005;Lim et al, 2005;Mulsow et al, 2005). It is tempting to speculate, therefore, that the antagonistic effects of telomerase and TGF-b on MAP kinase and protein kinase C signaling may account for the antagonistic effects of telomerase and TGF-b on gene expression.…”

Section: Discussionmentioning

confidence: 95%

Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-β signaling

et al. 2006

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Here, we show that ectopic expression of the catalytic subunit of mouse telomerase (mTert) confers a growth advantage to primary murine embryonic fibroblasts (MEFs), which have very long telomeres, as well as facilitates their spontaneous immortalization and increases their colony-forming capacity upon activation of oncogenes. We demonstrate that these telomere lengthindependent growth-promoting effects of mTert overexpression require catalytically active mTert, as well as the formation of mTert/Terc complexes. The gene expression profile of mTert-overexpressing MEFs indicates that telomerase enhances growth in these cells through the repression of growth-inhibiting genes of the transforming growth factor-beta (TGF-b) signaling network. We functionally validate this result by showing that mTert abrogates the growth-inhibitory effect of TGF-b in MEFs, thus demonstrating that telomerase increments the proliferative potential of primary mouse embryonic fibroblasts by targeting the TGF-b pathway.

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TGF-β1 induces cardiac hypertrophic responses via PKC-dependent ATF-2 activation

Cited by 89 publications

References 23 publications

Angiotensin II-induced cardiomyocyte hypertrophy in vitro is TAK1-dependent and Smad2/3-independent

Angiotensin II-induced cardiomyocyte hypertrophy in vitro is TAK1-dependent and Smad2/3-independent

pCREB is Involved in Neural Induction of Mouse Embryonic Stem Cells by RA

Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-β signaling

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