MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases

Climent, Montserrat; Viggiani, Giacomo; Lin, Chen‐Yong; Coulis, Gérald; Castaldi, Alessandra

doi:10.3390/ijms21124370

Cited by 101 publications

(81 citation statements)

References 239 publications

(298 reference statements)

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“…It was reported that production of reactive oxygen species (ROS) upregulated miR-206 expression (57,58). Interestingly, IL-13, a type 2 cytokine, promotes ROS production in airway epithelial cells (59).…”

Section: Discussionmentioning

confidence: 99%

Epithelial microRNA-206 targets CD39/extracellular ATP to upregulate airway IL-25 and TSLP in type 2-high asthma

et al. 2021

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The epithelial cell-derived cytokines IL-25, IL-33 and TSLP initiate type inflammation in allergic diseases including asthma. However, the signaling pathway regulating these cytokines expression remains elusive. Since microRNAs are pivotal regulators of gene expression, we profiled microRNA expression in bronchial epithelial brushings from type 2-low and type 2-high asthma patients. MiR-206 was the most highly expressed epithelial microRNA in type 2-high asthma relative to type 2-low asthma but was downregulated in both subsets compared with healthy controls. CD39, an ectonucleotidase degrading ATP, was a target of miR-206 and upregulated in asthma. Allergen-induced acute extracellular ATP accumulation led to miR-206 downregulation and CD39 upregulation in human bronchial epithelial cells, forming a feedback loop to eliminate excessive ATP. Airway ATP levels were markedly elevated and strongly correlated with IL-25 and TSLP expression in asthma patients. Intriguingly, airway miR-206 antagonism increased Cd39 expression, reduced ATP accumulation, suppressed Il-25, Il-33, Tslp expression and group 2 innate lymphoid cell expansion, and alleviated type 2 inflammation in a mouse model of allergic airway inflammation. In contrast, airway miR-206 overexpression had opposite effects. Overall, epithelial miR-206 upregulates airway IL-25, TSLP expression by targeting CD39-extracellular ATP axis, which represents a novel therapeutic target in type 2-high asthma.

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Section: Discussionmentioning

confidence: 99%

Epithelial microRNA-206 targets CD39/extracellular ATP to upregulate airway IL-25 and TSLP in type 2-high asthma

et al. 2021

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“…One of the main risk factors of BPD in premature infants is hyperoxia exposure, which signi cantly increase the risk of pneumonia and retinopathy of prematurity (ROP). It has been previously shown that hyperoxia induced lung injury (or oxygen toxicity) is mainly mediated by reactive oxygen species (ROS), while ROS production is related to infection, in ammatory reaction and mitochondrial respiration [27,28]. Choo-Wing et al [29] found that the combined treatment of hyperoxia exposure and interferon gamma on neonatal mice caused ERS to occur in lung tissues, as well as upregulated the expression of cyclooxygenase-2 (Cox2) and apoptosis of epithelial cells at the same time.…”

Section: Discussionmentioning

confidence: 99%

The Function Role of Ubiquitin Proteasome Pathway in the ER Stress-induced AECII Apoptosis during Hyperoxia Exposure

Zhu

et al. 2021

Preprint

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Backgroud: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in premature infants, characterized by alveolar dysplasia and pulmonary microvascular remodeling. In the present study, we have investigated the functional roles of ubiquitin proteasome pathway (UPP) in BPD, and its relationship with endoplasmic reticulum stress (ER stress, ERS) mediated AECII apoptosis. Methods: A hyperoxia-induced BPD rat model was constructed and the pathologic changes of lung tissues were evaluated by Hematoxylin-Eosin staining. Cell apoptosis and protein expression were determined by TUNEL assay and Western blotting, respectively. Further reagent kit with specific fluorescent substrate was utilized to measure the activity of 20s proteasome. Meanwhile, AECII were cultured in vitro and exposed to hyperoxia. AECII apoptosis were measured by flow cytometry. In contrast, MG132 treatment was induced to explore ubiquitin proteasome pathway during hyperoxia exposure on AECII apoptosis and ERS sensors expression.Results: A significant increase in apoptosis and total ubiquitinated proteins expression were observed in BPD rats and AECII culture, and the change of UPP was associated with ERS. In order to confirm the role of UPP in AECII apoptosis of BPD, AECII cells were treated by MG132 with the concentration of 10 μmol/L under hyperoxia exposure. We found that the proteins expression of GRP-78, PERK, ATF4, ATF6 and CHOP, as well as AECII apoptosis were increased following MG132 treatment. Furthermore, the relatively up-regulated in the levels of total ubiquitinated proteins expression and 20S proteasome activity were correlated with increased ERS sensors expression. Conclusions: Our findings indicate that UPP may participate in the ERS-induced AECII apoptosis under hyperoxia condition.

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“…In endothelial cells, miR-199a expression has been shown to promote cell survival, proliferation, migration, and tube formation [ 126 ]. miR-199a expression plays a protective role in the cardiomyocytes of MI, and downregulation of miR-199a expression is observed in the presence of ROS [ 127 ]. Meanwhile, other recent studies suggest the opposite opinion and deny the cardioprotective function demonstrated by miR-199a.…”

Section: Cvd-related Mirnas Target Enos and Sirt1mentioning

confidence: 99%

Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

Lee

2021

Antioxidants

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Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.

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MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases

Cited by 101 publications

References 239 publications

Epithelial microRNA-206 targets CD39/extracellular ATP to upregulate airway IL-25 and TSLP in type 2-high asthma

Epithelial microRNA-206 targets CD39/extracellular ATP to upregulate airway IL-25 and TSLP in type 2-high asthma

The Function Role of Ubiquitin Proteasome Pathway in the ER Stress-induced AECII Apoptosis during Hyperoxia Exposure

Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

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