MicroRNA-34a Promotes Endothelial Dysfunction and Mitochondrial-mediated Apoptosis in Murine Models of Acute Lung Injury

Shah, Dilip; Das, Pragnya; Alam, Mohammad Afaque; Mahajan, Nidhi; Romero, Freddy; Shahid, Mohd; Singh, Harpreet; Bhandari, Vineet

doi:10.1165/rcmb.2018-0194oc

Cited by 28 publications

(24 citation statements)

References 40 publications

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“…Mitochondria-modulated cell death contributes to OC and resistance to cisplatin (29). It is widely recognized that changes in Bax and Bcl-2 expression levels regulate matrix metalloproteinases (30,31). The present results indicated that elevation of the Bax/Bcl-2 ratio stimulated changes in mitochondrial permeability, and that OC cells treated by apigenin had an increase in the proportion of green signals, thus indicating that the mitochondrial membrane was depolarized in the cell population.…”

Section: Discussionsupporting

confidence: 52%

Apigenin induces apoptosis and counteracts cisplatin‑induced chemoresistance via Mcl‑1 in ovarian cancer cells

Ding

Yao

et al. 2020

Exp Ther Med

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Ovarian cancer (OC) is one of the prominent causes of mortality in female patients diagnosed with gynecologic malignancies. While it has previously been demonstrated that apigenin inhibits cell growth in colon and breast cancer cells, the effect of apigenin in OC cells is not fully understood. Therefore, the aim of the present study was to investigate the impact of apigenin on cell death and resistance to cisplatin in OC cells. It was found that apigenin inhibited proliferation, hindered cell cycle progression and promoted SKOV3 cell apoptosis. Moreover, these effects were also observed in cisplatin-resistant SKOV3/DDP cells. Furthermore, apigenin reduced the mitochondrial transmembrane potential, and elevated the ratios of cleaved caspase-3/caspase-3 and Bax/Bcl-2 in the two cell types. Reverse transcription-quantitative PCR and western blotting results demonstrated that apigenin significantly downregulated Mcl-1 at the transcriptional and translational levels in SKOV3 and SKOV3/DDP cells, which was responsible for its cytotoxic functions and chemosensitizing effects. Collectively, the present results identified the impact of apigenin on OC cell death and resistance to cisplatin, and the potential molecular mechanisms. However, additional studies are required to further elucidate the underlying mechanisms.

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Section: Discussionsupporting

confidence: 52%

Apigenin induces apoptosis and counteracts cisplatin‑induced chemoresistance via Mcl‑1 in ovarian cancer cells

Ding

Yao

et al. 2020

Exp Ther Med

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“…MLECs were purchased from Cell Biologics (Chicago, IL) and maintained in cell culture medium (Cell Biologics, Chicago, IL) as previously described [24]. Exposure to hyperoxia was achieved by leaving the plates inside a tightly sealed modular chamber (Stem Cell Technologies, Vancouver, Canada) filled with 100% oxygen for 16 h.…”

Section: Cell Culturementioning

confidence: 99%

“…When MLECs had reached a confluence of approximately 70%, they were transferred to an antibiotic free growth medium (Cell Biologics, Chicago, IL) and transfected with 50 nM miR-451 inhibitor (catalog ID: IH-310630-07, Dharmacon, Lafayette, CO) using the Lipofectamine 3000 kit (Invitrogen, Thermo Fisher Scientific, Waltham, MA). Dosage of the inhibitor was determined based on the results of previous work published by our group [24,25]. Cells were then replated and incubated at 37°C for 24 h prior to exposure to either RA or hyperoxia.…”

Section: In-vitro Inhibition Of Mir-451mentioning

confidence: 99%

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Inhibition of microRNA-451 is associated with increased expression of Macrophage Migration Inhibitory Factor and mitigation of the cardio-pulmonary phenotype in a murine model of Bronchopulmonary Dysplasia

et al. 2020

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Background: Macrophage migration inhibitory factor (MIF) has been implicated as a protective factor in the development of bronchopulmonary dysplasia (BPD) and is known to be regulated by . The aim of this study was to evaluate the role of miR-451 and the MIF signaling pathway in in vitro and in vivo models of BPD. Methods: Studies were conducted in mouse lung endothelial cells (MLECs) exposed to hyperoxia and in a newborn mouse model of hyperoxia-induced BPD. Lung and cardiac morphometry as well as vascular markers were evaluated. Results: Increased expression of miR-451 was noted in MLECs exposed to hyperoxia and in lungs of BPD mice. Administration of a miR-451 inhibitor to MLECs exposed to hyperoxia was associated with increased expression of MIF and decreased expression of angiopoietin (Ang) 2. Treatment with the miR-451 inhibitor was associated with improved lung morphometry indices, significant reduction in right ventricular hypertrophy, decreased mean arterial wall thickness and improvement in vascular density in BPD mice. Western blot analysis demonstrated preservation of MIF expression in BPD animals treated with a miR-451 inhibitor and increased expression of vascular endothelial growth factor-A (VEGF-A), Ang1, Ang2 and the Ang receptor, Tie2. Conclusion: We demonstrated that inhibition of miR-451 is associated with mitigation of the cardio-pulmonary phenotype, preservation of MIF expression and increased expression of several vascular growth factors.

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“…There were several lines of evidence suggesting that miRNAs were involved in the endothelial injury. For example, miRNA‐34a promoted endothelial dysfunction in murine models of acute lung injury, 20 and increased expression of miR‐483‐3p alleviated vascular endothelial injury in type 2 diabetes 21 . However, the role of plasma‐derived exosomal miRNAs in MPA endothelial injury has not been reported so far.…”

Section: Discussionmentioning

confidence: 99%

Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients

et al. 2020

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Microscopic polyangiitis (MPA) is a systemic autoimmune disease that primarily affects the small and medium blood vessels. Endothelial injury is one of the pathological hallmarks of MPA. However, the pathogenesis for this has not yet been fully elucidated. Exosomal microRNAs (miRNAs) have recently emerged as a new molecular pattern involved in the endothelial injury in other diseases. Hence, we speculated that MPA plasma-derived exosomes (MPA-exo) could induce the endothelial injury, which was likely to be aroused by the dysregulated exosomal miRNAs in MPA. In the present study, plasma-derived exosomes were isolated and identified. MPA-exo could be internalized by human renal glomerular endothelial cells (HRGECs) in vitro and induced HRGECs injury. Subsequently, a series of differentially expressed miRNAs in MPAexo were identified by high-throughput sequencing analysis. Further bioinformatics analysis for the target genes of these differentially expressed miRNAs showed a potential mechanism for their possible role in MPA endothelial injury. Notably, we revealed a considerable correlation between miR-185-3p, miR-125a-3p, and clinical parameters. In conclusion, the current study revealed that differentially expressed miRNAs in MPA-exo are associated with the endothelial injury. Our results suggested that these miRNAs and their target genes might be involved in the inflammation process of MPA. K E Y W O R D Shigh-throughput sequencing, microRNA profile, plasma exosomes 6216 | WANG et Al.

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MicroRNA-34a Promotes Endothelial Dysfunction and Mitochondrial-mediated Apoptosis in Murine Models of Acute Lung Injury

Cited by 28 publications

References 40 publications

Apigenin induces apoptosis and counteracts cisplatin‑induced chemoresistance via Mcl‑1 in ovarian cancer cells

Apigenin induces apoptosis and counteracts cisplatin‑induced chemoresistance via Mcl‑1 in ovarian cancer cells

Inhibition of microRNA-451 is associated with increased expression of Macrophage Migration Inhibitory Factor and mitigation of the cardio-pulmonary phenotype in a murine model of Bronchopulmonary Dysplasia

Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients

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