FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism

Joki, Yusuke; Ohashi, Koji; Yuasa, Daisuke; Shibata, Rei; Ito, Masanori; Matsuo, Kazuhiro; Kambara, Takahiro; Uemura, Yoshiko; Hayakawa, Shinobu; Hiramatsu-Ito, Mizuho; Kanemura, Noriyoshi; Ogawa, Hayato; Daida, Hiroyuki; Murohara, Toyoaki; Ouchi, Noriyuki

doi:10.1016/j.bbrc.2015.02.081

Cited by 101 publications

(92 citation statements)

References 33 publications

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“…Moreover, FGF21 can protect the heart from apoptosis by activation of the Erk1/2-p38 MAPK-AMPK survival pathway (Zhang et al 2015a). Evidence from these reports confirmed that FGF21 plays a critical role in myocardial protection and anti-apoptosis following myocardial injury (Patel et al 2014, Joki et al 2015, Zhang et al 2015a). Due to the potential cardioprotective benefits of FGF21, it is possible that FGF21 could be used to prevent and/or treat the myocardial apoptosis due to I/R injury or MI.…”

Section: Molecular Basis Of Anti-apoptosis Signaling Cascades Of Fgf21mentioning

confidence: 84%

“…It was also shown that these protective effects could be reversed by SiRNA-FGF21 intravenously injected 1 day prior to MI (Liu et al 2012). Moreover, in chronic MI (2 weeks) C57BL6 and adiponectin-KO mice models it was demonstrated that FGF21 protein derived from skeletal muscles protected the heart from apoptosis through adiponectin signaling (Joki et al 2015). In addition, FGF21 100 mg/kg per day s.c. injections for 4 weeks could protect the abdominal aorta from arteriosclerotic lesions through lipid regulation and ER stress induced vascular cell apoptosis in the ApoE-KO model (Wu et al 2014).…”

Section: Effects Of Fgf21 On Myocyte Apoptosis and Myocardial Infarctionmentioning

confidence: 97%

“…In the heart, FGF21 ligands act via the FGFR1c (Suzuki et al 2008, Liu et al 2013, Planavila et al 2013, Wu et al 2014, and FGFR3 (Suzuki et al 2008, Liu et al 2013, utilizing b-Klotho as a co-receptor (Suzuki et al 2008, Liu et al 2013, Planavila et al 2013. Endogenous and exogenous FGF21 plays an anti-apoptotic role in both in vitro and in vivo models, partially through the adiponectin signaling cascade (Joki et al 2015). Recent studies found that FGF21 protects against isoproterenol (ISO) induced cardiac hypertrophy by activating anti-oxidative pathways (Planavila et al 2013(Planavila et al , 2014 and promoting FAO (Planavila et al 2013).…”

Section: Effects Of Fgf21 On the Heartmentioning

confidence: 99%

“…The FGF21 ligand is produced from several organs such as the liver and adipose tissue (Ito et al 2000), skeletal muscle (Joki et al 2015), and the heart (Nishimura et al 2000, Kharitonenkov 2009, Planavila et al 2013, Patel et al 2014. To activate FGF21 signaling, FGF21 binds to FGFR1c with its C-terminus, and also with b-Klotho as its co-receptor with its N-terminus, to form the FGFR/ b-Klotho complex (Kharitonenkov 2008, Suzuki et al 2008, Yie et al 2009, Ding et al 2012, Hale et al 2012.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, FGF21 also protects the heart from apoptosis and remodeling through the activation of adiponectin release to activate the adiponectin signaling pathways (Joki et al 2015). Currently, the biological and pharmacological mechanism of FGF21 in cardioprotection is still to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Effects of fibroblast growth factor 21 on the heart

Tanajak¹,

Chattipakorn²

2015

Journal of Endocrinology

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Fibroblast growth factor 21 (FGF21) is a novel polypeptide ligand that has been shown to be involved in several physiological and pathological processes including regulation of glucose and lipids as well as reduction of arteriosclerotic plaque formation in the great vessels. It has also been shown to exert cardioprotective effects in myocardial infarction, cardiac ischemiareperfusion injury, cardiac hypertrophy and diabetic cardiomyopathy. Moreover, FGF21 protects the myocardium and great arteries by attenuating remodeling, inflammation, oxidative stress and also promoting the energy supply to the heart through fatty acid b-oxidation. This growing evidence emphasizes the important roles of FGF21 in cardioprotection. This review comprehensively summarizes and discusses the consistent and inconsistent findings regarding the beneficial effects of FGF21 on the heart available from both basic research and clinical reports. The details of the signaling, biological and pharmacological effects of FGF21 with regard to its protection of the heart are also presented and discussed in this review.

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Section: Molecular Basis Of Anti-apoptosis Signaling Cascades Of Fgf21mentioning

confidence: 84%

Section: Effects Of Fgf21 On Myocyte Apoptosis and Myocardial Infarctionmentioning

confidence: 97%

Section: Effects Of Fgf21 On the Heartmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of fibroblast growth factor 21 on the heart

Tanajak¹,

Chattipakorn²

2015

Journal of Endocrinology

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Alteration in serum concentrations of FGF19, FGF21, and FGF23 in patients with urothelial carcinoma

Chiu

et al. 2018

BioFactors

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Fibroblast growth factors (FGF) 19, 21, and 23 have been reported as functional factors in human metabolic diseases and malignancies. We performed a prospective survey to compare circulating FGF levels in urothelial carcinoma (UC) patients and normal controls. Between 2016 and 2017, 39 patients with UC of the urinary bladder or upper urinary tract who received surgical intervention were included. All the serum samples were obtained before surgeries. The control group included 28 healthy volunteers. Analysis of the circulating FGF19, 21, and 23 levels among all 67 subjects, as well as a subgroup analysis of the 39 UC patients were performed. The median levels of serum FGF19, 21, and 23 in the UC patients were 84.2, 505.3, and 117.6 pg/mL, respectively, which were statistically different from levels found in the healthy controls (P = 0.015, <0.001 and < 0.001, respectively). In the subgroup analysis, the FGF19 and FGF21 levels were significantly higher in end‐stage renal disease UC patients, while FGF21 was also higher in the UC patients with cardiovascular diseases and history of recurrent UC. In the receiver operating characteristic (ROC) curve analysis, FGF19, 21, and 23 were all significant predictors of UC [area under the curve (AUC)] 0.674, P = 0.015; AUC 0.918, P < 0.001; AUC 0.897, P < 0.001, respectively). In UC patients, serum FGF19 level was significantly lower, while FGF21 and 23 were significantly higher, than respective levels in healthy controls. All three markers may serve as good predictors of UC occurrence, and FGF21 level was associated with disease recurrence. © 2018 BioFactors, 45(1):62–68, 2019

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Fibroblast growth factor 21 protects against pathological cardiac remodeling by modulating galectin‐3 expression

Sun

Jin

Bai

et al. 2019

J of Cellular Biochemistry

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Background/Aims: Fibroblast growth factor 21 (FGF21) plays a protective role in ischemia/reperfusion induced cardiac injury. However, the exact molecular mechanism of FGF21 action remains unclear. This study was designed the protective effect of FGF21 on the heart and its mechanism.Method: Adenovirus vector expressing FGF21 or control β-galactosidase was injected into the myocardium of mice. Myocardial injury was observed by tissue staining and immunohistochemical staining. The expression level of caspases-3 and galectin-3 in myocardial cells were observed by immunoblotting. Then, hypoxia-induced cell model was established. Small interfering RNA (SiRNA) and plasmid were transfected into H9c2 using Lipofectamine 2000 reagent (Invitrogen). The expression levels of galectin-3, ECM and cystatin-3 in cells were observed by immunoblotting, and the relationship between fibroblast growth factor 21 and galectin-3 was analyzed. Result: Cell test in vitro showed that FGF21 could inhibit apoptosis and decrease the expression of ECM (ColIaI, fibronectin, and alpha-SMA) under hypoxia. Western blot data showed that hypoxia-induced cell damage increased galectin-3 levels, while FGF21 decreased galactose lectin-3 levels. In addition, inhibition of galactose agglutinin-3 expression by siRNA enhanced the cardioprotective effect of FGF21, while overexpression of galectin-3 reduced the cardioprotective effect of fibroblast growth factor 21.Conclusion: FGF21 may be a novel therapy for hypoxia-induced cardiac injury by regulating the expression of galectin-3. K E Y W O R D Sbiomarkers, cardioprotection, fibroblast growth factor-21, galectin-3

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FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism

Cited by 101 publications

References 33 publications

Effects of fibroblast growth factor 21 on the heart

Effects of fibroblast growth factor 21 on the heart

Alteration in serum concentrations of FGF19, FGF21, and FGF23 in patients with urothelial carcinoma

Fibroblast growth factor 21 protects against pathological cardiac remodeling by modulating galectin‐3 expression

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