Endothelium-targeted overexpression of constitutively active FGF receptor induces cardioprotection in mice myocardial infarction

Matsunaga, Shinsaku; Okigaki, Mitsuhiko; Takeda, Mitsuo; Matsui, Akihiro; Honsho, Shoken; Katsume, Asako; Kishita, Eigo; Che, Jishan; Kurihara, Tatsuya; Adachi, Yasushi; Mansukhani, Alka; Kobara, Miyuki; Matoba, Yoshiaki; Tatsumi, Tomohide; Matsubara, Hiroaki

doi:10.1016/j.yjmcc.2009.01.015

Cited by 39 publications

(43 citation statements)

References 39 publications

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“…The mice showed decreased infarct size and improved cardiac performance compared with wild type (Wt) mice when acute cardiac ischemia was induced [16].…”

Section: Introductionmentioning

confidence: 95%

“…FGFR2 Tg mice were prepared as described previously [16]. C57BL=6 mice congenic for the ly5 locus (B6-ly5.1 mice) were bred and maintained at the animal center of Kansai Medical University (Moriguchi City, Osaka, Japan).…”

Section: Micementioning

confidence: 99%

“…Recently, we established mutant mice in which a constitutively active form of FGFR2 mutant was caused to be overexpressed using the Tie2 promoter (FGFR2 Tg mice) [16]. The mice showed decreased infarct size and improved cardiac performance compared with wild type (Wt) mice when acute cardiac ischemia was induced [16].…”

Section: Introductionmentioning

confidence: 99%

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Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

Shigematsu

Shi²,

Okigaki³

et al. 2010

Stem Cells and Development

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Fibroblast growth factor (FGF) and FGF receptor (FGFR) are expressed in various cells including endothelial progenitor cells and hematopoietic cells. The interaction between FGF and FGFR is associated with the proliferation, migration, and survival of these cells. In this report, we examined the effects of FGFR2 signaling on hematopoiesis in immature hematopoietic cells, using mutant mice in which a constitutively active form of FGFR2 mutant was caused to be overexpressed by the Tie2 promoter (FGFR2 Tg mice). Under normal conditions, hematopoiesis of FGFR2 Tg mice and wild type (Wt) mice do not differ significantly, except for the weight and cell numbers of the thymus. However, the c-kit + Sca-1 + lineage À bone marrow cells (BMCs) of FGFR2 Tg mice facilitate the formation of colony-forming units of culture. When these BMCs were transplanted into the recipient bone marrow (intra-bone marrow-bone marrow transplantation), there was better reconstitution of donor hematopoietic cells. In the in vitro experiment, the c-kit + Sca-1 + lineage À BMCs from FGFR2 Tg mice showed fewer apoptotic cells than those from Wt mice. These results suggest that the antiapoptotic effect of FGFR2 signaling facilitates the hematopoiesis of FGFR2 Tg mice.

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“…The mice showed decreased infarct size and improved cardiac performance compared with wild type (Wt) mice when acute cardiac ischemia was induced [16].…”

Section: Introductionmentioning

confidence: 95%

Section: Micementioning

confidence: 99%

See 1 more Smart Citation

Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

Shigematsu

Shi²,

Okigaki³

et al. 2010

Stem Cells and Development

Self Cite

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“…The operation was performed as previously described (23). The procedures are described in detail in the Supplemental Material.…”

Section: Surgical Procedures Of MI In Micementioning

confidence: 99%

“…Histochemical staining of myocytes was performed as previously described (21,23). This is described in detail in the Supplemental Material.…”

Section: Surgical Procedures Of MI In Micementioning

confidence: 99%

p53 and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress

Kimata

Matoba

Iwai-Kanai

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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meostasis is altered in heart failure and may play an important role in pathogenesis. p53 has been implicated in heart failure, and although its role in regulating tumorigenesis is well characterized, its activities on cellular metabolism are just beginning to be understood. We investigated the role of p53 and its transcriptional target gene TP53-induced glycolysis and apoptosis regulator (TIGAR) in myocardial energy metabolism under conditions simulating ischemia that can lead to heart failure. Expression of p53 and TIGAR was markedly upregulated after myocardial infarction, and apoptotic myocytes were decreased by 42% in p53-deficient mouse hearts compared with those in wild-type mice. To examine the effect of p53 on energy metabolism, cardiac myocytes were exposed to hypoxia. Hypoxia induced p53 and TIGAR expression in a p53-dependent manner. Knockdown of p53 or TIGAR increased glycolysis with elevated fructose-2,6-bisphosphate levels and reduced myocyte apoptosis. Hypoxic stress decreased phosphocreatine content and the mitochondrial membrane potential of myocytes without changes in ATP content, the effects of which were prevented by the knockdown of TIGAR. Inhibition of glycolysis by 2-deoxyglucose blocked these bioenergetic effects and TIGAR siRNA-mediated prevention of apoptosis, and, in contrast, overexpression of TIGAR reduced glucose utilization and increased apoptosis. Our data demonstrate that p53 and TIGAR inhibit glycolysis in hypoxic myocytes and that inhibition of glycolysis is closely involved in apoptosis, suggesting that p53 and TIGAR are significant mediators of cellular energy homeostasis and cell death under ischemic stress.TP53-induced glycolysis and apoptosis regulator; hypoxia; metabolism; mitochondria; glycolysis DESPITE SIGNIFICANT THERAPEUTIC ADVANCES, heart failure (HF) remains a leading cause of morbidity and mortality (12, 32). Numerous studies (10, 26) have identified altered cardiac energy homeostasis as a consistent feature of HF. Recently, metabolic-based therapies have attracted much interest as a new approach for the treatment of HF. For example, a metabolic modulator, trimetazidine, shifts the energy source from free fatty acid toward predominantly glucose utilization and improves the cardiac function of patients with idiopathic dilated cardiomyopathy (35). Transgenic mice overexpressing glucose transporter (GLUT)-1 have increased glucose uptake, preserved contractile reserve, and resist the development of HF by chronic pressure overload or ischemic injury (17,20). Based on these promising findings, additional insights into the mechanisms regulating cardiac energy metabolism may be helpful for further advancing our treatment regimens.Cardiac myocytes are known to undergo apoptosis in hypoxia and ischemia-reperfusion (6, 34). Reducing apoptotic cell death and the effect of remodeling after myocardial infarction (MI) have been primary goals, as extensive MI causes severe congestive HF (15). p53 regulates apoptosis, DNA repair, cell cycle progression, and senescence in response...

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A novel long noncoding RNA FAF inhibits apoptosis via upregulating FGF9 through PI3K/AKT signaling pathway in ischemia–hypoxia cardiomyocytes

Shi

Wang

Sun

et al. 2019

Journal Cellular Physiology

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Long noncoding RNAs (lncRNAs) have been increasingly considered to play an important role in the pathological process of various cardiovascular diseases, which often bind to the proximal promoters of the protein-coding gene to regulate the protein expression. However, the functions and mechanisms of lncRNAs in cardiomyocytes have not been fully elucidated. High-throughput RNA sequencing was performed to identify the differently expressed lncRNAs and messenger RNAs (mRNAs) between acute myocardial infarction (AMI) rats and healthy controls. One novel lncRNA FGF9-associated factor (termed FAF) and mRNAs in AMI rats were verified by bioinformatics, real-time polymerase chain reaction or western blot. Moreover, RNA fluorescence in situ hybridization was performed to determine the location of lncRNA. Subsequently, a series of in vitro assays were used to observe the functions of lncRNA FAF in cardiomyocytes. The expression of lncRNA FAF and FGF9 were remarkably decreased in ischemiahypoxia cardiomyocytes and heart tissues of AMI rats. Overexpression of FAF could significantly inhibit cardiomyocytes apoptosis induced by ischemia and hypoxia. Conversely, knockdown of lncRNA FAF could promote apoptosis in ischemia-hypoxia cardiomyocytes. Moreover, overexpression of lncRNA FAF could also increase the expression of FGF9. Knockdown of the FGF9 expression could promote apoptosis in cardiomyocytes with the insult of ischemia and hypoxia, which was consistent with the effect of lncRNA FAF overexpression on cardiomyocyte apoptosis. Mechanistically, FGF9 inhibited cardiomyocytes apoptosis through activating signaling tyrosine kinase FGFR2 via phosphoinositide 3-kinase/protein kinase B signaling pathway. Thus, lncRNA FAF plays a protective role in ischemia-hypoxia cardiomyocytes and may serve as a treatment target for AMI. K E Y W O R D S cardiomyocytes apoptosis, FGF9, ischemia-hypoxia, lncRNA FAF Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Shi HJ, Wang MW, Sun JT, et al. A novel long noncoding RNA FAF inhibits apoptosis via upregulating FGF9 through PI3K/AKT signaling pathway in ischemia-hypoxia cardiomyocytes.

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Endothelium-targeted overexpression of constitutively active FGF receptor induces cardioprotection in mice myocardial infarction

Cited by 39 publications

References 39 publications

Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

p53 and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress

A novel long noncoding RNA FAF inhibits apoptosis via upregulating FGF9 through PI3K/AKT signaling pathway in ischemia–hypoxia cardiomyocytes

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