MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases

Lee, Ding Yu; Lin, Ting Er; Lee, Chih I.; Zhou, Jing; Huang, Yi; Lee, Pei Ling; Shih, Yu Tsung; Chien, Shu; Chiu, Jeng Jiann

doi:10.1073/pnas.1621425114

Cited by 52 publications

(70 citation statements)

References 21 publications

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“…Our scRNAseq and scATACseq results are consistent with our previous gene array results using the endothelial-enriched RNA samples in bulk obtained from the same mouse PCL model . As shown in our bulk RNA data and other reports (Ajami et al, 2017;Jiang et al, 2014;Lee et al, 2017;Ni et al, 2010;Son et al, 2013;Wang et al, 2016;Wang et al, 2006), our singlecell data showed expected changes in many well-known flow sensitive genes including Klf2, Klf4,Nos3,Klk10,Angpt2,Ctgf,Bmp4,Timp3,Tgfb1,Thsp1,Col1a1,Tagln,Acta2,Cnn1,and Snai1. The current study also showed that d-flow induced inflammatory and proliferative pathways, consistent with our bulk RNA array result (Ni et al, 2010), further demonstrating the validity of our single-cell results. One of the major limitations of the bulk RNA study was the inability to ascertain the cell-types where the gene changes were occurring.…”

Section: Accessibility and Co-accessibility Analyses Reveal Flow-depesupporting

confidence: 89%

Endothelial reprogramming by disturbed flow revealed by single-cell RNA and chromatin accessibility study

Andueza

Kumar

Kim

et al. 2020

Preprint

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SUMMARYDisturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNAseq) and scATACseq study using endothelial-enriched single-cells from the left- and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flow in RCA) using the mouse partial carotid ligation (PCL) model. We found 8 EC clusters along with immune cells, fibroblasts, and smooth muscle cells. Analyses of marker genes, pathways, and pseudo-time revealed that ECs are highly heterogeneous and plastic. D-flow induced a dramatic transition of ECs from atheroprotective phenotypes to pro-inflammatory, mesenchymal (EndMT), hematopoietic stem cells, endothelial stem/progenitor cells, and an unexpected immune cell-like (EndICLT) phenotypes. While confirming KLF4/KLF2 as s-flow-sensitive transcription factor binding site, we also found those sensitive to d-flow (RELA, AP1, STAT1, and TEAD1). D-flow reprograms ECs from atheroprotective to pro-atherogenic phenotypes including EndMT and potentially EndICLT.

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Section: Accessibility and Co-accessibility Analyses Reveal Flow-depesupporting

confidence: 89%

Endothelial reprogramming by disturbed flow revealed by single-cell RNA and chromatin accessibility study

Andueza

Kumar

Kim

et al. 2020

Preprint

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“…Based on the integrated miRNA and mRNA analysis together with target prediction and the importance of the TH signaling pathway during metamorphosis, a network of differentially expressed miRNAs and differentially expressed genes in the TH pathway was constructed. The expression of miR-10a was switched on by RARα , a hormone receptor modulated by RXRα [ 60 ]. Because RXRα and TRα were upregulated by T3 during metamorphosis and TRα was the target gene of miR-10a, T3- RXRα-RARα- miR-10a- TRα played the negative feedback role in M. fissipes metamorphosis.…”

Section: Discussionmentioning

confidence: 99%

Identification and differential regulation of microRNAs during thyroid hormone-dependent metamorphosis in Microhyla fissipes

et al. 2018

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BackgroundAnuran metamorphosis, which is obligatorily initiated and sustained by thyroid hormone (TH), is a dramatic example of extensive morphological, biochemical and cellular changes occurring during post-embryonic development. Thus, it provides an ideal model to understand the actions of the hormone and molecular mechanisms underlying these developmental and apoptotic processes. In addition to transcriptional factors, microRNAs (miRNAs) play key roles in diverse biological processes via post-transcriptional repression of mRNAs. However, the possible role of miRNAs in anuran metamorphosis is not well understood. Screening and identification of TH-responding miRNAs are required to reveal the integrated regulatory mechanisms of TH during metamorphosis. Given the specific role of TRs during M. fissipes metamorphosis and the characteristics of M. fissipes as an ideal model, Illumina sequencing technology was employed to get a full scope of miRNA in M. fissipes metamorphosis treated by T3.ResultsMorphological and histological analysis revealed that 24 h T3 treatment M. fissipes tadpoles resembled that at the climax of natural metamorphosis. Thus, small RNA libraries were constructed from control and 24 h T3 treatment groups. A total of 164 conserved miRNAs and 36 predicted novel miRNAs were characterized. Furthermore, 5′ first and ninth nucleotides of miRNAs were significantly enriched in U in our study. In all, 21 miRNAs were differentially expressed between the T3 and control groups (p < 0.01). A total of 10,206 unigenes were identified as target genes of these differentially expressed miRNAs. KEGG pathway analysis indicated that the most overrepresented miRNA target genes were enriched in the “PI3k-Akt signaling pathway”. In addition, a network associated with the TH signaling pathway provides an opportunity to further understand the complex biological processes that occur in metamorphosis.ConclusionsWe identified a large number of miRNAs during M. fissipes metamorphosis, and 21 of them were differentially expressed in the two groups that represented two different metamorphic stages. These miRNAs may play important roles during metamorphosis. The study gives us clues for further studies of the mechanisms of anuran metamorphosis and provides a model to study the mechanism of TH-affected biological processes in humans.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4848-x) contains supplementary material, which is available to authorized users.

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“…Specifically, PS induces the expression, nuclear localization, and association of RAR-a with the binding enhancer retinoid X receptor-a, to augment the RAR-a binding to RARE and hence miR-10a expression. In contrast, OS induces the association of RAR-a with histone deacetylases HDAC-3/5/7, which impairs the RARa-directed miR-10a expression (35). In cultured human aortic endothelial cells, miR-10a impairs NF-kB-mediated expression of E-selectin, VCAM-1, MCP-1, IL-6, and IL-8 through targeting 2 key regulators of IkB-a degradation: TAK1 and b-TRC (33).…”

Section: Mirnas Target the Cytoplasmic Axis Of The Nf-kb Pathwaymentioning

confidence: 98%

Endothelial microRNAs regulating the NF‐κB pathway and cell adhesion molecules during inflammation

2018

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The surface of endothelial cells is covered with cell adhesion molecules, including E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM- 1) , that mediate the adhesion and extravasation of leukocytes and play pivotal roles in inflammatory response. microRNAs (miRNAs) regulate the expression of these important cell adhesion molecules through two distinct major mechanisms, namely via modulating the proinflammatory NF-κB pathway, which controls their transcription, and via directly targeting them. The present review highlights the role of various miRNAs in controlling the expression of E-selectin, ICAM-1, and VCAM-1: a type of regulation that can be harnessed for therapeutic prevention of inflammation-associated diseases such as atherosclerosis and sepsis. The roles of secreted miRNAs as paracrine regulators, and cell adhesion molecule-based miRNA delivery are also addressed.-Zhong, L., Simard, M. J., Huot, J. Endothelial microRNAs regulating the NF-κB pathway and cell adhesion molecules during inflammation.

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MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases

Cited by 52 publications

References 21 publications

Endothelial reprogramming by disturbed flow revealed by single-cell RNA and chromatin accessibility study

Endothelial reprogramming by disturbed flow revealed by single-cell RNA and chromatin accessibility study

Identification and differential regulation of microRNAs during thyroid hormone-dependent metamorphosis in Microhyla fissipes

Endothelial microRNAs regulating the NF‐κB pathway and cell adhesion molecules during inflammation

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