SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene

Nakaoka, Yoshikazu; Shioyama, Wataru; Kunimoto, Satoshi; Arita, Yoh; Higuchi, Kaori; Yamamoto, Kaori; Fujio, Yasushi; Nishida, Keigo; Kimura, Tadashi; Hirota, Hisao; Yamauchi–Takihara, Keiko; Hirano, Toshio; Komuro, Issei; Mochizuki, Naoki

doi:10.1016/j.yjmcc.2010.03.001

Cited by 17 publications

(18 citation statements)

References 37 publications

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“…We previously reported that Gab1 is critically involved in activation of ERK5 after stimulation with leukemia inhibitory factor in cardiomyocytes. 18,19 Therefore, we performed ERK5 in vitro kinase assay using glutathione S-transferase (GST) fusion protein containing transactivating domain of myocyte enhancer factor 2 (MEF2C) (GST-MEF2C) as a substrate. HGF induced the strongest activation of ERK5 in HUVECs among these agonists ( Figure 2H and 2I).…”

Section: Hgf Induces the Strongest Tyrosine Phosphorylation Of Gab1 Amentioning

confidence: 99%

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Docking Protein Gab1 Is an Essential Component of Postnatal Angiogenesis After Ischemia via HGF/c-Met Signaling

Shioyama¹,

Nakaoka²,

Higuchi³

et al. 2011

Circulation Research

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Rationale: Grb2-associated binder (Gab) docking proteins, consisting of Gab1, Gab2, and Gab3, have crucial roles in growth factor-dependent signaling. Various proangiogenic growth factors regulate angiogenesis and endothelial function. However, the roles of Gab proteins in angiogenesis remain elusive.Objective: To elucidate the role of Gab proteins in postnatal angiogenesis. Methods and Results: Endothelium-specific Gab1 knockout (Gab1ECKO) mice were viable and showed no obvious defects in vascular development. Therefore, we analyzed a hindlimb ischemia (HLI) model of control, Gab1ECKO, or conventional Gab2 knockout (Gab2KO) mice. Intriguingly, impaired blood flow recovery and necrosis in the operated limb was observed in all of Gab1ECKO, but not in control or Gab2KO mice. Among several proangiogenic growth factors, hepatocyte growth factor (HGF) induced the most prominent tyrosine phosphorylation of Gab1 and subsequent complex formation of Gab1 with SHP2 (Src homology-2-containing protein tyrosine phosphatase 2) and phosphatidylinositol 3-kinase subunit p85 in human endothelial cells (ECs). Gab1-SHP2 complex was required for HGF-induced migration and proliferation of ECs via extracellular

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Section: Hgf Induces the Strongest Tyrosine Phosphorylation Of Gab1 Amentioning

confidence: 99%

“…18,19 On the other hand, it has been reported that Gab1 has a role for VEGF-dependent signaling in the in vitro experiments using ECs. 20 -22 However, the in vivo role of Gab proteins in angiogenesis has not been addressed to date.…”

mentioning

confidence: 99%

Docking Protein Gab1 Is an Essential Component of Postnatal Angiogenesis After Ischemia via HGF/c-Met Signaling

Shioyama¹,

Nakaoka²,

Higuchi³

et al. 2011

Circulation Research

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“…RhoA/ ROCK pathway activation plays an important role in Ang II-mediated cardiac hypertrophy and fibrosis . The inhibition of endothelin-1-induced RhoA activation can inhibit skeletal a-actin (a-SKA) expression and suppress cardiomyocyte hypertrophy (Nakaoka et al 2010). The blockade of rhoA associated p-38 and JNK MAPK signaling has been demonstrated to inhibit the hypertrophic marker (BNP) and attenuate Ang II-induced cardiac hypertrophy (Ye et al 2010).…”

Section: Fasudil Prevents Eeet-induced Cardiac Hypertrophymentioning

confidence: 99%

“…The STAT3-dependent pathway was reported to cause cardiac myocyte hypertrophy (Kunisada et al 1998). The ERK5 pathway was also induced by gp130 and played a crucial role in eccentric hypertrophy (Nakaoka et al 2010). MEK5-ERK5 signaling was triggered by IL-6 induced serial assembly of sarcomeres and eccentric cardiac hypertrophy that progressed to dilated cardiomyopathy and sudden death (Nicol et al 2001;Chen et al 2007).…”

Section: Fasudil Prevents Eeet-induced Cardiac Hypertrophymentioning

confidence: 99%

Fasudil, a Rho-kinase inhibitor, protects against excessive endurance exercise training-induced cardiac hypertrophy, apoptosis and fibrosis in rats

Huang

et al. 2011

Eur J Appl Physiol

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Excessive endurance exercise training (EEET) is accompanied by cardiac remodeling, changes in ventricular function and increased heart failure risk. Fasudil, a potent Rho-kinase inhibitor, has been demonstrated to blunt cardiomyocyte hypertrophy, cardiac remodeling, and heart failure progression in pre-clinical trials and has been approved for clinical use in Japan. We examined the in vivo bioefficacy of fasudil against EEET-induced cardiac remodeling and the underlying molecular mechanisms. Male Sprague-Dawley rats were randomly divided into three groups: sedentary control (SC), EEET, and EEET with fasudil treatment (EEET-F). Rats in EEET and EEET-F groups ran on a motorized treadmill for 12 weeks. The results revealed that EEET increased myocardial hypertrophy (LV weight/tibial length), myocyte cross-sectional area, hypertrophy-related pathways (IL6/STAT3-MEK5-ERK5, calcineurin-NFATc3, p38 and JNK MAPK), hypertrophic markers (ANP/BNP), pro-apoptotic molecules (cytochrome C, cleaved caspase-3 and PARP), and fibrosis-related pathways (FGF-2-ERK1/2) and fibrosis markers (uPA, MMP-9 and -2). These pathways were then expressed lower in the EEET-F group when compared with the EEET group. The cardiac hypertrophic level, apoptotic pathway and fibrosis signaling were further inhibited in the fasudil-treated group. We systematically investigated the possible signaling pathways leading to EEET-induced cardiac hypertrophy, apoptosis and fibrosis. We also provide evidence for the novel function of fasudil in suppressing EEET-induced cardiac remodeling and impairment by multiple mechanisms, which suggests that the RhoA signaling pathway contributes to EEET-induced cardiac remodeling and dysfunction.

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“…CITED4 knockdown below basal levels still enhanced LIF-induced elongation, indicating basal CITED4 expression in the myocytes that protects against elongation signaling. Previous work has demonstrated the importance of ERK5 signaling in LIF-induced elongation [147]. LIF also significantly increased abundance of C/EBPβ mRNA, a gene down-regulated in exercise-induced hypertrophy [28].…”

Section: Discussionmentioning

confidence: 88%

Systems Analysis of the Cardiac Myocyte Hypertrophy Signaling Network

Ryall¹

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SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene

Cited by 17 publications

References 37 publications

Docking Protein Gab1 Is an Essential Component of Postnatal Angiogenesis After Ischemia via HGF/c-Met Signaling

Docking Protein Gab1 Is an Essential Component of Postnatal Angiogenesis After Ischemia via HGF/c-Met Signaling

Fasudil, a Rho-kinase inhibitor, protects against excessive endurance exercise training-induced cardiac hypertrophy, apoptosis and fibrosis in rats

Systems Analysis of the Cardiac Myocyte Hypertrophy Signaling Network

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