MicroRNA Regulation of Acute Lung Injury and Acute Respiratory Distress Syndrome

Rajasekaran, Subbiah; Pattarayan, Dhamotharan; Rajaguru, P.; Gandhi, P. S. Sudhakar; Thimmulappa, Rajesh K.

doi:10.1002/jcp.25316

Cited by 122 publications

(102 citation statements)

References 103 publications

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“…Fluid-based miRNA (serum, saliva, sputum, cerebrospinal fluid, plasma, whole blood, and urine) profiling could provide invaluable information for studies where the disease is not derived from only one type of cell or a specific type of cell. This possibility has opened doors for non-invasive diagnostic techniques in various disease states [49], [50], [51], [52], [53]. Hence miRNAs are considered good therapeutic targets in cancer and cardiovascular disease [54], [55], [56].…”

Section: Introductionmentioning

confidence: 99%

Redox regulation of microRNAs in endometriosis-associated pain

2017

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Endometriosis is a chronic, painful condition with unknown etiology. A differential expression of microRNAs in the endometriotic tissues from women with endometriosis with pain compared to those without suggested a plausible role for miRNA or epigenetic mechanisms in the etiology of endometriotic pain. The peritoneal milieu is involved in maintenance of endometriotic lesion and nociception. We recently showed the mechanistic role for oxidized-lipoproteins (ox-LDLs) present in peritoneal fluid (PF) in endometriosis and pain. We explored the possibility of ox-LDLs modulating the expression of miRNAs in a manner similar to PF from women with endometriosis. Expression levels of miRNAs and their predicted nociceptive and inflammatory targets were determined in PF and ox-LDL treated human endometrial cell-lines. Samples from IRB-approved and consented patients with and without endometriosis or pain were used. These were compared to endometrial cell-lines treated with various forms of oxidized-lipoproteins. RNA (including miRNAs) were isolated from treated endometrial cells and expression levels were determined using commercial miRNome arrays. Cell lysates were used in immunoblotting for inflammatory proteins using a protein array. Twenty miRNAs including isoforms of miR-29, miR-181 and let-7 were mutually differentially expressed in cells treated with PF from endometriosis patients with pain and those treated with ox-LDL components. The ox-LDLs and endo-PF treatment also produced significant overexpression of microRNA predicted target genes nerve growth factor, interleukin-6 and prostaglandin E synthase and overexpression of their downstream protein targets Mip1α and MCP1. This study showed similarities between miRNA regulation in PF from endometriotic women and ox-LDLs present in abundance in the PF of these women. Key miRNAs responsible for targeting nociceptive and inflammatory molecules were downregulated in the presence of ox-LDLs and endo-PF, thus playing a role in the etiology of endometriotic pain. These redox-sensitive miRNAs can be of potential use as targets in the treatment of endometriosis-associated pain.

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Section: Introductionmentioning

confidence: 99%

Redox regulation of microRNAs in endometriosis-associated pain

2017

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“…miRNAs are important regulatory RNAs, which mainly function in repressing gene expression at the post-transcriptional level by binding to the 3′-UTR of target mRNAs through base pairing12. However, some researchers found out that miRNAs may also positively regulate target mRNAs3. Substantial evidence indicated that miRNA dysregulation is related to a number of human diseases, such as cancer45.…”

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confidence: 99%

Network Consistency Projection for Human miRNA-Disease Associations Inference

Liao

et al. 2016

Sci Rep

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Prediction and confirmation of the presence of disease-related miRNAs is beneficial to understand disease mechanisms at the miRNA level. However, the use of experimental verification to identify disease-related miRNAs is expensive and time-consuming. Effective computational approaches used to predict miRNA-disease associations are highly specific. In this study, we develop the Network Consistency Projection for miRNA-Disease Associations (NCPMDA) method to reveal the potential associations between miRNAs and diseases. NCPMDA is a non-parametric universal network-based method that can simultaneously predict miRNA-disease associations in all diseases but does not require negative samples. NCPMDA can also confirm the presence of miRNAs in isolated diseases (diseases without any known miRNA association). Leave-one-out cross validation and case studies have shown that the predictive performance of NCPMDA is superior over that of previous method.

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“…Growing evidence indicates that dysregulation of miRNAs is closely associated with the pathogenesis of diseases including lung diseases [8].…”

Section: Introductionmentioning

confidence: 99%

MiR-135a Protects Vascular Endothelial Cells Against Ventilator-Induced Lung Injury by Inhibiting PHLPP2 to Activate PI3K/Akt Pathway

Yan

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Loss of endothelial barrier function plays an important role in the development of ventilator-induced lung injury (VILI). This study aimed to investigate the effects of miR135a on VILI in a model of mechanical stretch (MS)-induced human umbilical vein endothelial cell (HUVEC) injury. Methods: HUVECs were randomly assigned to 7 groups: blank, negative control (NC), NC+MS, miR135a over-expression (mi-miR135a), mi-miR135a + MS, miR135a silencing (si-miR135a) and si-miR135a + MS groups. MS was induced by subjecting cells to cyclic stretch at 20% stretch for 4 h. After 24 h, levels of reactive oxygen species (ROS) were measured by DCFH-DA fluorescence intensity. Apoptosis was measured using annexin V-FITC/propidium iodide assay with flow cytometry. Inflammatory cytokine levels were determined by ELISA. Barrier integrity was determined using FITC-conjugated dextran assay. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2 and Bax were examined using western blotting. The interaction between miR135a and PHLPP2 was evaluated by dual-luciferase reporter assay. Results: Our results showed that MS reduced cell numbers, increased the number of apoptotic cells, increased ROS, barrier dysfunction and inflammatory cytokines in HUVECs, and reduced p-PI3K and p-Akt expression; silencing of miR135a worsened MS-induced HUVEC injury. However, miR135a over-expression protected HUVECs against MS-induced increases in apoptotic cells, ROS, barrier dysfunction and inflammatory cytokines, which were accompanied by activation of the PI3K/Akt signaling pathway. Simultaneous silencing of miR135a and PHLPP2 partially salvaged the effects of miR135a silencing, and miR135a was found to interact with PHLPP2. Conclusion: miR135a may protect HUVECs from MS-induced injury by inhibiting PHLPP2 to activate PI3k/Akt signaling pathway.

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MicroRNA Regulation of Acute Lung Injury and Acute Respiratory Distress Syndrome

Cited by 122 publications

References 103 publications

Redox regulation of microRNAs in endometriosis-associated pain

Redox regulation of microRNAs in endometriosis-associated pain

Network Consistency Projection for Human miRNA-Disease Associations Inference

MiR-135a Protects Vascular Endothelial Cells Against Ventilator-Induced Lung Injury by Inhibiting PHLPP2 to Activate PI3K/Akt Pathway

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