Inducible miR-145 expression by HIF-1α protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment

Sun, Nianzi; Meng, Fanyan; Xue, Ning; Pang, Guanghui; Wang, Qingxin; Ma, Heng

doi:10.5603/cj.a2017.0105

Cited by 22 publications

(16 citation statements)

References 19 publications

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“…Previous studies confirm that the Pi3K/aKT pathway can activate HiF-1α, thus playing an important role in cell growth and cell survival (22,30). research has shown that the activation of the Pi3K/aKT/HiF-1α pathway mediates protection against lung i/r injury (28), and the upregulation and activation of the Pi3K/aKT/HiF-1α pathway is involved in the protective effects of micrornas on cardiomyocytes (37). Troxerutin preconditioning has been shown to protect against Mi/r injury by inhibiting apoptosis and activating the Pi3K/aKT pathway (34).…”

Section: Discussionmentioning

confidence: 85%

Troxerutin attenuates oxygen‑glucose deprivation and reoxygenation‑induced oxidative stress and inflammation by enhancing the PI3K/AKT/HIF‑1α signaling pathway in H9C2 cardiomyocytes

et al. 2020

Mol Med Rep

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Myocardial ischemia-reperfusion (Mi/r) injury is a complex pathological process that occurs when tissues are reperfused following a prolonged period of ischemia. Troxerutin has been reported to have cardioprotective functions. However, the underlying mechanism by which troxerutin protects against Mi/r injury has not been fully elucidated. The aim of the present study was to explore whether troxerutin-mediated protection against oxygen-glucose deprivation/reoxygenation (oGd/r)-induced H9c2 cell injury was associated with the inhibition of oxidative stress and the inflammatory response by regulating the Pi3K/aKT/hypoxia-inducible factor-1α (HiF-1α) signaling pathway. The results of the present study suggested that troxerutin pretreatment prevented the oGd/r-induced reduction in cell viability, and the increase in lactate dehydrogenase activity and apoptosis. Troxerutin reversed oGd/r-induced the inhibition of the Pi3K/aKT/HiF-1α signaling pathway as demonstrated by the increased expression of Pi3K and HiF-1α, and the increased ratio of phosphorylated aKT/aKT. lY294002, a selective Pi3K inhibitor, inhibited the Pi3K/aKT/HiF-1α signaling pathway and further attenuated the protective effect of troxerutin against oGd/r-induced H9c2 cell damage. Furthermore, small interfering (si)rna-mediated knockdown of HiF-1α reduced troxerutin-induced protection against oGd/r injury. Troxerutin pretreatment alleviated oGd/r-induced oxidative stress, as demonstrated by the reduced generation of reactive oxygen species and malonaldehyde content, and the increased activities of superoxide dismutase and glutathione peroxidase, which were reduced by HiF-1α-sirna. Troxerutin-induced decreases in the levels of interleukin (il)-1β, il-6 and tumor necrosis factor-α in oGd/r conditions were also reduced by HiF-1α-sirna. The results from the present study indicated that troxerutin aggravated oGd/r-induced H9c2 cell injury by inhibiting oxidative stress and the inflammatory response. The primary underlying protective mechanism of troxerutin was mediated by the activation of the Pi3K/aKT/HiF-1α signaling pathway.

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Section: Discussionmentioning

confidence: 85%

Troxerutin attenuates oxygen‑glucose deprivation and reoxygenation‑induced oxidative stress and inflammation by enhancing the PI3K/AKT/HIF‑1α signaling pathway in H9C2 cardiomyocytes

et al. 2020

Mol Med Rep

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“…In gastric cancer, miR-145 could inhibit the tumor cell migration by targeting MYO6 [28]. In neuropathic pain, miR-145 could ameliorate this perplex by inhibiting inflammatory responses through the mTOR signaling pathway [35]. In the present study, we predicted the target gene of miR-145, and proved that FOXO1 was a target gene in VECs.…”

Section: Discussionmentioning

confidence: 52%

MicroRNA-145 is involved in endothelial cell dysfunction and acts as a promising biomarker of acute coronary syndrome

Sun

2020

Eur J Med Res

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Background: Acute coronary syndrome (ACS) is a serious type of cardiovascular diseases. This study aimed to investigate the expression patterns and clinical value of in ACS patients, and further uncover the function of miR-145 in ACS rats. Methods:Quantitative real-time PCR was used to estimate the expression of miR-145. Diagnostic value of miR-145 was evaluated, and its correlation with endothelial injury marker (vWF and H-FABP) and pro-inflammatory cytokines (IL-6 and TNF-α) was analyzed. Coronary artery ligation was adopted to construct the ACS rat model, and the effects of miR-145 on endothelial injury, inflammation and vascular endothelial cells (VECs) biological function were examined.Results: Downregulated expression of miR-145 was found in the ACS serum samples compared with the healthy controls. The expression of miR-145 was proved to be a diagnostic biomarker and negatively correlated with vWF, H-FABP, IL-6 and TNF-α. The similar serum expression trends of miR-145 in ACS patients were also observed in the ACS rats, and the overexpression of miR-145 could decrease the elevated vWF, H-FABP, IL-6 and TNF-α in the animal model. Moreover, the upregulation of miR-145 in VECs led to promoted proliferation and migration. The bioinformatics prediction data and luciferase report results indicated that FOXO1 was a direct target of miR-145. Conclusions:In conclusion, it was hypothesized that serum decreased expression of miR-145 may serve as a potential diagnostic biomarker in ACS patients. Overexpression of miR-145 may improve the endothelial injury and abnormal inflammation through targeting FOXO1, indicating that miR-145 serves as a candidate therapeutic target of ACS. CW, Lim DS. Comparison of ticagrelor versus prasugrel for inflammation, vascular function, and circulating endothelial progenitor cells in diabetic patients with non-ST-segment elevation acute coronary syndrome requiring coronary stenting: a prospective, randomized, crossover trial. -217 inhibits proliferation, migration, and invasion via targeting AKT3 in thyroid cancer. Biomed Pharmacother. 2017;95:1718-24.

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“…Cardiac remodeling, characterized by reduced heart function and excessive interstitial collagen, 3 is a common pathological phenomenon among post‐MI patients. miR‐145 is widely known as an anticancer noncoding RNA, 29 and previous studies have shown that it has cardioprotective effects, inhibiting inflammation and apoptosis 9‐11 and accelerating autophagy 30 in cardiomyocytes. Moreover, overexpression of miR‐145 in the MI heart significantly improved cardiac function and decreased the size of the MI area 11,30 .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies mainly focused on the myocardial cells, where upregulation of miR-145 delayed the development of cardiovascular diseases. Sun and coworkers [9][10][11] demonstrated that miR-145 inhibited hypoxia-induced cardiomyocyte injury by targeting programmed cell death 4. Recently, Huang et al 12 found that miR-145 could ameliorate cardiac fibrosis, and the long-noncoding RNA metastasis-associated lung adenocarcinoma transcript 1, which function as a miR-145 sponge and promoted cardiac fibrosis via regulation of transforming growth factor-β1.…”

Section: Introductionmentioning

confidence: 99%

miR‐145 attenuates cardiac fibrosis through the AKT/GSK‐3β/β‐catenin signaling pathway by directly targeting SOX9 in fibroblasts

Cui¹,

Liu²,

Bo³

et al. 2020

J of Cellular Biochemistry

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Myocardial infarction (MI) will inevitably result in cardiac fibrosis. In this study, we investigated the effect of microRNA-145 (miR-145) and transcription factor sex-determining region Y box 9 (SOX9) in the production of cardiac fibrosis induced by MI. MI rat models were established by left anterior descending coronary artery (LAD) occlusion. Four weeks after LAD, the cardiac fibrosis level was assessed by Masson's trichrome staining. Cardiac fibroblasts (CFs) exposed to hypoxia were used to simulate MI-induced fibrosis. Flow cytometry, cell counting kit-8, and transwell assays were used to examine changes in CF apoptosis, proliferation, and migration, respectively. miR-145 expression was measured by quantitative real-time polymerase chain reaction. Immunofluorescence and Western blot analysis were performed to determine the relative expression of proteins. In comparison to the sham-operated group, the expression of miR-145 was significantly downregulated in the infarction peripheral area, whereas, SOX9 was upregulated. In the infarcted heart, the overexpression of miR-145 significantly ameliorated cardiac fibrosis and cardiac function, and there was a negative correlation between miR-145 and SOX9 expressions in hypoxic CFs in vitro. In addition, SOX9 was verified to be a functional target of miR-145. Overexpression of miR-145 or inhibition of SOX9 decreased CF proliferation, migration, and fibrosis, but augmented their apoptotic rate. Moreover, the upregulation of miR-145 or suppression of SOX9 inhibited AKT and β-catenin signaling in hypoxic CFs. Taken together, this study highlights a potential treatment for cardiac fibrosis through the targeted regulation of SOX9 by miR-145, and our findings indicate that miR-145 exerts anti-fibrotic effects in MI via the negative regulation of SOX9 and its downstream AKT/GSK-3β/β-catenin pathways.

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Inducible miR-145 expression by HIF-1α protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment

Abstract: (Cardiol J 2018; 25, 2: 268-278)

Cited by 22 publications

References 19 publications

Troxerutin attenuates oxygen‑glucose deprivation and reoxygenation‑induced oxidative stress and inflammation by enhancing the PI3K/AKT/HIF‑1α signaling pathway in H9C2 cardiomyocytes

Troxerutin attenuates oxygen‑glucose deprivation and reoxygenation‑induced oxidative stress and inflammation by enhancing the PI3K/AKT/HIF‑1α signaling pathway in H9C2 cardiomyocytes

MicroRNA-145 is involved in endothelial cell dysfunction and acts as a promising biomarker of acute coronary syndrome

miR‐145 attenuates cardiac fibrosis through the AKT/GSK‐3β/β‐catenin signaling pathway by directly targeting SOX9 in fibroblasts

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