EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model

Liang, Dandan; Zhong, Peng; Hu, Jie; Lin, Feng; Qian, Yuanyuan; Xu, Zheng; Wang, Jingying; Zeng, Chunlai; Li, Xiaokun; Liang, Guang

doi:10.1016/j.yjmcc.2015.02.029

Cited by 55 publications

(70 citation statements)

References 34 publications

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“…One week later, blood glucose levels were measured, and mice with a fasting-blood glucose of N12 mmol/l were considered diabetic and were used for further study. The DR model was established as previously described (19). The EC and RP cells were isolated according to the protocol as previously described (20,21).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1

Fang

Guo

et al. 2017

Oncology Letters

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Abstract. Diabetic retinopathy (DR) is a sight-threatening complication of diabetes. IRS-1 was predicted to be the target gene of microRNA-126 (miR-126). The present study was designed to illustrate the involvement of miR-126 in the regulation of DR via targeting IRS-1. The present study revealed that the expression of miR-126 was significantly decreased while IRS-1 expression was increased in endothelial cells (ECs) and retinal pericytes (RPs) from a DR mouse model compared with healthy controls. Furthermore, a luciferase reporter assay confirmed the interaction between miR-126 and IRS-1. Following transfection with anmiR-126 mimic or miR-126 inhibitor, overexpression of miR-126 was demonstrated to suppress the invasion and viability of ECs and RPs and to inhibit the IRS-1 and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway protein expression levels, with inhibition of miR-126 leading to reverse results. Furthermore, transfection with small interfering RNA targeting IRS-1 altered the miR-126-induced effects observed in ECs, indicating that miR-126 may suppress angiogenesis in DR via inhibition ofIRS-1 expression. Taken together, the results of the present study suggested that miR-126 affected the expression of IRS-1, resulting in downregulated expression of PI3K/Akt pathway proteins, and also suppressed cell invasion and viability. These results may provide a potential therapeutic strategy for DR.

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Section: Methodsmentioning

confidence: 99%

MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1

Fang

Guo

et al. 2017

Oncology Letters

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“…Increased EGFR activity is reported in mice with streptozotocin induced type I diabetes, concomitant with ER stress, cardiac fibrosis and collagen deposition (Galan et al, 2012;Liang et al, 2015). Systemic inhibition of EGFR mitigated these effects of diabetes, though the high dose of AG1478 (10 mg/kg/day) also reduced the extent of hyperglycemia, complicating interpretation.…”

Section: Hypertrophy/heart Failurementioning

confidence: 99%

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Reichelt

O’Brien

Thomas

et al. 2017

The International Journal of Biochemistry & Cell Biology

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“…Moreover, inhibition of EGFR by specific tyrosine kinase inhibitor AG1478 significantly decreases the angiotensin II-mediated synthesis of Transforming Growth Factor (TGF)-β and fibronectin by cardiac fibroblasts15. Recently, our group found that EGFR inhibition significantly attenuated streptozotocin-induced diabetic heart injuries16. These studies suggest that EGFR antagonism may be an effective drug target for cardiac hypertrophy and remodeling.…”

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confidence: 99%

EGFR Inhibition Blocks Palmitic Acid-induced inflammation in cardiomyocytes and Prevents Hyperlipidemia-induced Cardiac Injury in Mice

Fang

Zhong

et al. 2016

Sci Rep

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Obesity is often associated with increased risk of cardiovascular diseases. Previous studies suggest that epidermal growth factor receptor (EGFR) antagonism may be effective for the treatment of angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy. This study was performed to demonstrate if EGFR plays a role in the pathogenesis of hyperlipidemia/obesity-related cardiac injuries. The in vivo studies using both wild type (WT) and apolipoprotein E (ApoE) knockout mice fed with high fat diet (HFD) showed the beneficial effects of small-molecule EGFR inhibitors, AG1478 and 542, against obesity-induced myocardial injury. Administration of AG1478 and 542 significantly reduced myocardial inflammation, fibrosis, apoptosis, and dysfunction in both two obese mouse models. In vitro, EGFR signaling was blocked by either siRNA silencing or small-molecule EGFR inhibitors in palmitic acid (PA)-stimulated cardiomyocytes. EGFR inhibition attenuated PA-induced inflammatory response and apoptosis in H9C2 cells. Furthermore, we found that PA-induced EGFR activation was mediated by the upstream TLR4 and c-Src. This study has confirmed the detrimental effect of EGFR activation in the pathogenesis of obesity-induced cardiac inflammatory injuries in experimental mice, and has demonstrated the TLR4/c-Src-mediated mechanisms for PA-induced EGFR activation. Our data suggest that EGFR may be a therapeutic target for obesity-related cardiovascular diseases.

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EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model

Cited by 55 publications

References 34 publications

MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1

MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

EGFR Inhibition Blocks Palmitic Acid-induced inflammation in cardiomyocytes and Prevents Hyperlipidemia-induced Cardiac Injury in Mice

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