Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway

Zheng, Tao; Yang, Jun; Zhang, Jing; Yang, Chaojun; Fan, Zhixing; Li, Qi; Zhai, Yueyang; Liu, Haiyin; Yang, Jian

doi:10.3389/fphar.2021.669146

Cited by 14 publications

(6 citation statements)

References 45 publications

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“…Interestingly, it has been proposed that oxidative stress after MI/RI causes aberrant ROS accumulation, aggravating the myocardial damage ( 28 ). Our latest findings suggested that increasing HO-1 enzyme activities suppressed the oxidative stress both in vivo and in vitro , and ultimately improved MI/RI ( 41 ). Besides, our unpublished data show that MA could also reduce I/R-induced oxidative stress through suppressing ROS over accumulation.…”

Section: Discussionmentioning

confidence: 93%

Maslinic Acid Attenuates Ischemia/Reperfusion Injury-Induced Myocardial Inflammation and Apoptosis by Regulating HMGB1-TLR4 Axis

et al. 2021

Front. Cardiovasc. Med.

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Aims: The inflammatory response and apoptosis are the major pathological features of myocardial ischemia/reperfusion injury (MI/RI). Maslinic acid (MA), a natural pentacyclic triterpene with various bioactivities, plays critical roles in the multiple cellular biological processes, but its protective effects on the pathophysiological processes of MI/RI have not been extensively investigated. Our study aimed to determine whether MA treatment alleviate ischemia/reperfusion (I/R)-induced myocardial inflammation and apoptosis both in vitro and in vivo, and further reveal the underlying mechanisms.Methods and results: An MI/RI rat model was successfully established by ligating the left anterior descending coronary artery and H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to mimic I/R injury. In addition, prior to H/R stimulation or myocardial I/R operation, the H9c2 cells or rats were treated with varying concentrations of MA or vehicle for 24 h and two consecutive days, respectively. In this study, our results showed that MA could obviously increase the cell viability and decrease the cardiac enzymes release after H/R in vitro. MA could significantly improve the H/R-induced cardiomyocyte injury and I/R-induced myocardial injury in a dose-dependent manner. Moreover, MA suppressed the expression of inflammatory cytokines (tumor necrosis factor alpha [TNF-α, interleukin-1β [IL-1β and interleukin-6 [IL-6]) and the expressions of apoptosis-related proteins (cleaved caspase-3 and Bax) as well as increased the levels of anti-apoptotic protein Bcl-2 expression both in vitro and in vivo. Mechanistically, MA significantly inhibited nuclear translocation of nuclear factor-κB (NF-κB) p65 after H/R via regulating high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4) axis.Conclusion: Taken together, MA treatment may alleviate MI/RI by suppressing both the inflammation and apoptosis in a dose-dependent manner, and the cardioprotective effect of MA may be partly attributable to the inactivation of HMGB1/TLR4/NF-κB pathway, which offers a new therapeutic strategy for MI/RI.

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Section: Discussionmentioning

confidence: 93%

Maslinic Acid Attenuates Ischemia/Reperfusion Injury-Induced Myocardial Inflammation and Apoptosis by Regulating HMGB1-TLR4 Axis

et al. 2021

Front. Cardiovasc. Med.

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“…However, the mediators linking FGF10-FGFR2b and Nrf2 signaling require further exploration. It was reported that FGF10/Akt/Nrf2 signaling is critical in oxidative stress-mediated myocardial ischemia-reperfusion injury ( 39 ). Moreover, the protective effect of FGF10 in hepatic ischemia-reperfusion injury relies on PI3K/Akt-dependent Nrf2 activation ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

FGF10 mediates protective anti-oxidative effects in particulate matter-induced lung injury through Nrf2 and NF-κB signaling

Wang¹,

Shi²,

Liu³

et al. 2022

Ann Transl Med

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Background: Particulate matter (PM), a well-known environmental pollutant, is an independent risk factor associated with the morbidity of various respiratory diseases. Oxidative stress is an important pathophysiological mechanism related to PM exposure, which mediates redox-sensitive inflammatory signaling, leading to lung injury. Fibroblast growth factor 10 (FGF10), a paracrine fibroblast growth factor that mediates mesenchymal to epithelial signaling, participates in epithelial repair during lung injury. However, whether FGF10-mediated repair in PM-induced lung injury is related to the regulation of oxidative stress remains to be elucidated. Methods:In vivo, the C57BL/6 mice were randomly divided, with intratracheal instillation of 5 mg/kg FGF10 1 h before 4 mg/kg PM for 2 consecutive days. In vitro, the BEAS-2B cells were pretreated with 10 ng/mL FGF10 before exposed to 200 µg/mL PM. Besides, the specific Nrf2 inhibitor ML385 was adopted in vitro. The harvested lung tissues were pathologic grading scored. The state of oxidative stress was assessed with dihydroethidium (DHE) staining, malondialdehyde (MDA) activity, hydrogen peroxide (H 2 O 2 ) assays and reactive oxygen species (ROS). The contents of IL-6 and IL-8 in bronchoalveolar lavage (BAL) as well as culture supernatant were quantified by ELISA. The protein levels of nuclear factor erythroid 2 related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling from lung tissue as well as cell lysate were determined by Western blot.Results: In this study, recombinant FGF10 administration relieved the degree of lung injury, which is characterized by bronchitis, in a mouse model of PM exposure. In addition, reduced ROS levels, which are indicative of restrained oxidative stress, were also observed. Moreover, two redox-sensitive signaling pathways, Nrf2 and NF-κB, were found to be differentially regulated by FGF10. Using a cellular model of PM exposure, we found that the anti-inflammatory effect of FGF10 on NF-κB signaling was mediated through the regulation of oxidative stress. The anti-oxidative effect relied on the stimulation of Nrf2 signaling. Blockade of Nrf2 signaling with ML385 significantly compromised the anti-inflammatory effect of FGF10.Conclusions: These results underscore that the protective anti-oxidative effects of FGF10 in lung injury are mediated by the stimulation of Nrf2 signaling and inhibition of the NF-κB pathway.

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“…TBHP is a hydroperoxide homologue, that includes a tert‐butyl side chain and forms a more stable radical species than hydroperoxide. In recent years, increasing number of studies used TBHP instead of hydroperoxide to establish cell apoptosis models (Bi et al, 2018; Wang et al, 2020; Zheng et al, 2021). Therefore, we used THBP as an oxidative stress inducer to elucidate the effects and mechanisms of Calycosin.…”

Section: Discussionmentioning

confidence: 99%

Calycosin protects against oxidative stress‐induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2

Ding

Chen

Deng

et al. 2022

Phytotherapy Research

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Myocardial infarction (MI) is the leading cause of death worldwide, and oxidative stress is part of the process that causes MI. Calycosin, a naturally occurring substance with cardioprotective properties, is one of the major active constituents in Radix Astragali. In this study, effect of Calycosin was investigated in vivo and in vitro to determine whether it could alleviate oxidative stress and oxidative stress‐induced cardiac apoptosis in neonatal cardiomyocytes (NCMs) via activation of aldehyde dehydrogenase 2 (ALDH2). Calycosin protected against oxidative stress and oxidative stress‐induced apoptosis in NCMs. Molecular docking revealed that the ALDH2‐Calycosin complex had a binding energy of −9.885 kcal/mol. In addition, molecular docking simulations demonstrated that the ALDH2‐Calycosin complex was stable. Using BLI assays, we confirmed that Calycosin could interact with ALDH2 (KD = 1.9 × 10−4 M). Furthermore, an ALDH2 kinase activity test revealed that Calycosin increased ALDH2 activity, exhibiting an EC50 of 91.79 μM. Pre‐incubation with ALDH2 inhibitor (CVT‐10216 or disulfiram) reduced the cardio‐protective properties Calycosin. In mice with MI, Calycosin therapy substantially reduced myocardial apoptosis, oxidative stress, and activated ALDH2. Collectively, our findings clearly suggest that Calycosin reduces oxidative stress and oxidative stress‐induced apoptosis via the regulation of ALDH2 signaling, which supports potential therapeutic use in MI.

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Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway

Cited by 14 publications

References 45 publications

Maslinic Acid Attenuates Ischemia/Reperfusion Injury-Induced Myocardial Inflammation and Apoptosis by Regulating HMGB1-TLR4 Axis

Maslinic Acid Attenuates Ischemia/Reperfusion Injury-Induced Myocardial Inflammation and Apoptosis by Regulating HMGB1-TLR4 Axis

FGF10 mediates protective anti-oxidative effects in particulate matter-induced lung injury through Nrf2 and NF-κB signaling

Calycosin protects against oxidative stress‐induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2

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