Egr-1 is involved in coronary microembolization-induced myocardial injury via Bim/Beclin-1 pathway-mediated autophagy inhibition and apoptosis activation

Wang, Xiantao; Wu, Xiaodan; Lu, Yan-qing; Sun, Yani; Zhu, Han-Hua; Liang, Jing; He, Wei; Li, Lang

doi:10.18632/aging.101616

Cited by 19 publications

(15 citation statements)

References 38 publications

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“…In our previous study, we demonstrated that silencing Egr-1 expression could increase autophagy, inhibit apoptosis, and improve cardiac function in a rat model of coronary microembolization [19]. In the present study, we demonstrated that overexpression of miR-30e-3p inhibited Egr-1 expression, as well as augment autophagy, reduced apoptosis, and alleviate cardiomyocyte injury after IH exposure.…”

supporting

confidence: 59%

“…Studies have demonstrated that Egr-1 is regulated by miRNAs in several cardiovascular diseases [17,18]. In our previous study, we demonstrated that Egr-1 expression levels were increased and involved in the regulation of autophagy and apoptosis in a rat model for coronary microembolization [19]. However, whether miR-30e-3p regulates autophagy and apoptosis via the modulation of Egr-1 in IH-exposed cardiomyocytes is yet to be deciphered.…”

Section: Introductionmentioning

confidence: 90%

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miR-30e-3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr-1 during Ischemia/Hypoxia

Wang

Sun

et al. 2020

BioMed Research International

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Background. Microvascular obstruction (MVO) can result in coronary microcirculation embolism and myocardial microinfarction. Myocardial injury induced by MVO is characterized by continuous ischemia and hypoxia of cardiomyocytes. Autophagy and apoptosis are closely associated with various cardiovascular diseases. Based on our previous study, we observed a decrease in miR-30e-3p expression and an increase in Egr-1 expression in a rat coronary microembolization model. However, the specific function of miR-30e-3p in regulating autophagy and apoptosis in an ischemia/hypoxia (IH) environment remains to be deciphered. We exposed cardiomyocytes to an IH environment and then determined whether miR-30e-3p was involved in promoting cardiomyocyte autophagy and inhibiting apoptosis by regulating Egr-1. Methods. Cardiomyocytes were isolated from rats for our in vitro study. miR-30e-3p was either overexpressed or inhibited by transfection with lentiviral vectors into cardiomyocytes. 3-Methyladenine (3-MA) was used to inhibit autophagy. RT-qPCR and western blotting were used to determine the expression levels of miR-30e-3p, Egr-1, and proteins related to the autophagy and apoptosis process. Autophagic vacuoles and autophagic flux were evaluated using transmission electron microscopy (TEM) and confocal microscopy, respectively. Cardiomyocyte viability was evaluated using the MTS assay. Cell injury was assessed by lactate dehydrogenase (LDH) leakage, and apoptosis was determined by flow cytometry. Results. Both miR-30e-3p expression and autophagy were significantly inhibited, and apoptosis was increased in cardiomyocytes after 9 hours of IH exposure. Overexpression of miR-30e-3p increased autophagy and inhibited apoptosis, as well as suppressed Egr-1 expression and decreased cell injury. In addition, inhibition of miR-30e-3p reduced autophagy and increased apoptosis and cell injury. Conclusions. miR-30e-3p may be involved in promoting cardiomyocyte autophagy and inhibiting apoptosis by indirectly regulating Egr-1 expression in an IH environment.

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supporting

confidence: 59%

Section: Introductionmentioning

confidence: 90%

miR-30e-3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr-1 during Ischemia/Hypoxia

Wang

Sun

et al. 2020

BioMed Research International

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“…Egr1 and Egr2 belong to early growth response protein 1/2. They can induce myocardial injury by regulating myocardial autophagy, cell death, and the progression of myocardial fibrosis (Wang et al, 2018;Cao et al, 2010). Nr4a3, a member of the NR4A orphan nuclear receptor, plays a protective role during acute myocardial infarction by suppressing inflammatory responses via the JAK2-STAT3/NF-kB pathway (Obana et al, 2010;.…”

Section: Discussionmentioning

confidence: 99%

STAT3 but not STAT5 contributes to the protective effect of electro-acupuncture against myocardial ischemia/reperfusion injury

Guo

Jing

Chen³

et al. 2020

Preprint

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Late remote ischemia preconditioning (RIPC) and electro-acupuncture (EA) have both been suggested to reduce injury caused by myocardial ischemia/reperfusion (I/R). Our previous study has found that cardioprotection in RIPC is STAT5-dependent. Here, we aim to observe the effects of electro-acupuncture pretreatment (EAP) on I/R in the presence or absence of STAT5 in mice and investigate whether the protection of EAP is in a STAT5-dependent manner. In this study, EAP decreased myocardial infarction size (IS) /total area (TA) and rate of cardiomyocyte apoptosis. STAT5 was activated by EAP in the Stat5fl/fl mice but not in the Stat5-cKO mice, whereas, STAT3 was activated by EAP only in the Stat5-cKO but not in the Stat5fl/fl mice. Differentially expressed genes (DEGs) regulated by EAP in the Stat5fl/fl and the Stat5-cKO mice were quite distinct, indicating that EAP may activate IL-6/STAT3 signal in the absence of Stat5, and that EAP-induced cardioprotection against myocardial I/R injury was correlated with the activation of anti-apoptotic signaling and cardiomyocyte-survival signaling. Our results, for the first time, demonstrated that the protective effect of EAP was attributed to, but not dependent on, STAT5.

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“…In Table 1 we list the sequences of the primer sequences in detail. The nal result was expressed by the fold difference between the expression level of each mRNA and that of the internal reference using the 2 ΔΔCt method [20]. All samples were measured 3 times.…”

Section: Rt-qpcrmentioning

confidence: 99%

The intervention of S1PR1/STAT3 signaling pathway by inhibiting the expression of STAT3 attenuates the valvular damage due to rheumatic heart disease

Xian¹,

Chen²,

Yi-ming³

et al. 2020

Preprint

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Background Rheumatic heart disease (RHD) is a social health problem that affects many patients every year, but its pathogenesis is still unclear. Recent studies have found that the sphingosine 1-phosphate receptor 1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is activated during the development of valvular damage caused by RHD. STAT3 plays an important role in the differentiation of CD4 + T cells into T helper 17 (Th17) cells, and Th17 cell-related cytokines are involved in the development of RHD. In this work, we investigated whether altering the S1PR1/STAT3 signaling pathway by inhibiting the expression of STAT3 attenuates valvular damage due to RHD. Methods Inactivated Group A streptococci (GAS) and complete Freund’s adjuvant (CFA) were used to establish the RHD rat model. STAT3-small interfering RNA (STAT3-siRNA) was used to directly inhibit the expression of STAT3 in the heart. Histological examination was used to evaluate the degree of inflammation and fibrosis in valve tissues. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the levels of interleukin (IL)-6 and IL-17 in serum and valve tissue. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the mRNA expression of S1PR1 and STAT3. Western blotting (WB) and immunohistochemistry were used to detect the protein expression of S1PR1, STAT3, phosphorylated (p-) STAT3, retinoic acid-related orphan receptor gamma T (RORγt). Results The expression of S1PR1 in valve tissues of RHD model rats was decreased. The degree of valvular inflammation and fibrosis of RHD model rats was increased. The levels of IL-6 and IL-17 in valves and serum of RHD model rats were increased as well as an increase of p-STAT3 in valve tissues. Inhibition of STAT3 by STAT3-siRNA decreased STAT3 expression and reduced the total amount of p-STAT3, resulting in decreased expression of IL-6, IL-17 and RORγt in valves and serum and reduced valvular inflammatory response and fibrosis. Conclusions These results suggest that inhibiting the expression of STAT3 in the heart may reduce the valvular damage caused by rheumatic heart disease.

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Egr-1 is involved in coronary microembolization-induced myocardial injury via Bim/Beclin-1 pathway-mediated autophagy inhibition and apoptosis activation

Cited by 19 publications

References 38 publications

miR-30e-3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr-1 during Ischemia/Hypoxia

miR-30e-3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr-1 during Ischemia/Hypoxia

STAT3 but not STAT5 contributes to the protective effect of electro-acupuncture against myocardial ischemia/reperfusion injury

The intervention of S1PR1/STAT3 signaling pathway by inhibiting the expression of STAT3 attenuates the valvular damage due to rheumatic heart disease

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