Identification and Functional Characterization of Hypoxia-Induced Endoplasmic Reticulum Stress Regulating lncRNA (HypERlnc) in Pericytes

Bischoff, Florian; Werner, Astrid; John, David; Boeckel, Jes‐Niels; Melissari, Maria-Theodora; Grote, Phillip; Glaser, Simone F.; Demolli, Shemsi; Uchida, Shizuka; Michalik, Katharina; Meder, Benjamin; Katus, Hugo A.; Haas, Jan; Chen, Wei; Pullamsetti, Soni Savai; Seeger, Werner; Zeiher, Andreas M.; Dimmeler, Stefanie; Zehendner, Christoph M.

doi:10.1161/circresaha.116.310531

Cited by 66 publications

(47 citation statements)

References 28 publications

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“…LncRNA LINC01619 regulates miR-27a/FoxO1 and ER stress-mediated podocyte injury in DKD [ 93 ]. LncRNAs (HypERlnc) regulated by hypoxia-induced ER stress are identified in pericytes [ 94 ]. Therefore, ER-stress-regulated lncRNAs may have important functions in pathogenesis of kidney diseases.…”

Section: Ncrnas In the Early Stage Of Dkdmentioning

confidence: 99%

Noncoding RNAs as therapeutic targets in early stage diabetic kidney disease

Kato

2018

Kidney Res Clin Pract.

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Diabetic kidney disease (DKD) is a major renal complication of diabetes that leads to renal dysfunction and end-stage renal disease (ESRD). Major features of DKD include accumulation of extracellular matrix proteins and glomerular hypertrophy, especially in early stage. Transforming growth factor-β plays key roles in regulation of profibrotic genes and signal transducers such as Akt kinase and MAPK as well as endoplasmic reticulum stress, oxidant stress, and autophagy related to hypertrophy in diabetes. Many drugs targeting the pathogenic signaling in DKD (mostly through protein-coding genes) are under development. However, because of the limited number of protein-coding genes, noncoding RNAs (ncRNAs) including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are attracting more attention as potential new drug targets for human diseases. Some miRNAs and lncRNAs regulate each other (by hosting, enhancing transcription from the neighbor, hybridizing each other, and changing chromatin modifications) and create circuits and cascades enhancing the pathogenic signaling in DKD. In this short and focused review, the functional significance of ncRNAs (miRNAs and lncRNAs) in the early stages of DKD and their therapeutic potential are discussed.

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Section: Ncrnas In the Early Stage Of Dkdmentioning

confidence: 99%

Noncoding RNAs as therapeutic targets in early stage diabetic kidney disease

Kato

2018

Kidney Res Clin Pract.

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“…The Dimmeler group has contributed much to our understanding of vascular homeostasis, and the mechanisms that go awry in the pathobiology of vascular disease. In the current investigation, they introduce an intriguing new determinant of pericyte behavior that becomes most apparent during hypoxia (1). …”

Section: Pericytes and Vascular Homeostasismentioning

confidence: 99%

A Missing LNC in Vascular Diseases

Cooke¹,

Leeper

2017

Circulation Research

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Pericytes are vascular smooth muscle cells that stabilize the endothelial networks that comprise the microvasculature. There is increased interest in the role that these cells play in maintaining the architecture, permeability, and remodeling of the microvasculature. Furthermore, these cells may be a source of regenerative cells that participate in the response to injury and ischemia. Bischoff and colleagues have comprehensively characterized a novel determinant of pericyte function, and suggest its possible role in heart failure.

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“…Another study demonstrated that lncRNA ENSG 00000262454 correlated with pericyte markers in idiopathic pulmonary arterial hypertension. 10) In the case of CTEPH, Josipovic, et al 11) found that lncRNA NONHSAT 073641 was upregulated in the vascular samples of pa-miRNA-genes-lncRNA NETWORK IN CTEPH tients with CTEPH and were important for endothelial angiogenic function. Competing endogenous RNAs (ceRNA) was found to lead to the hypothesis that lncRNA could interact with the gene through microRNA (miRNA) by competing for endogenous inhibition.…”

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confidence: 99%

miRNA-PDGFRB/HIF1A-lncRNA CTEPHA1 Network Plays Important Roles in the Mechanism of Chronic Thromboembolic Pulmonary Hypertension

Wang

Liu

et al. 2019

Int. Heart J.

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Our previous studies have revealed that long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and genes were abnormally expressed in the pulmonary artery tissues of the chronic thromboembolic pulmonary hypertension (CTEPH) patients. We aim to establish the CTEPH-related miRNA-gene-lncRNA network for finding the core genes and associated miRNA and lncRNA in CTEPH patients.Firstly, the target genes of differential miRNAs were predicted by searching TargetScan databases, and the predicted target genes were intersected with the mRNAs from the gene chip. Secondly, the intersective genes were analyzed by the Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway software for obtaining differential intersective genes and then establish the miRNA-gene networks. Thirdly, the possible genes regulated by the differential lncRNAs from the gene chip were intersected with the above-screened mRNA to build the lncRNA-mRNA networks. Subsequently, the miRNA-gene-lncRNA networks were constructed according to the two networks above(miRNA-gene networks and lncRNA-mRNA networks). Finally, the core genes of the networks in the experimental group were screened according to Diffk > 0.6 and used to construct the miRNA-core gene-lncRNA networks of CTEPH.The pathway network, miRNA-mRNA network, lncRNA-mRNA networks, and miRNA-gene-lncRNA networks were successfully constructed. The core genes of the miRNA-gene-lncRNA networks (Diffk > 0.6) were the human Beta-type platelet-derived growth factor receptor (PDGFRB) and hypoxia-inducible factor-1a (HIF-1 A), the miRNAs-PDGFRB-lncRNAs and miRNAs-HIF1A-lncRNAs networks were constructed. Finally, miRNA-149-5p-PDGFRB-TCONS_l2_00020587-XLOC_l2_010723 and miRNA-338-5p/miRNA-199b-5p-HIF1 A-TCONS_l2_00020587-XLOC_l2_010723 were found in the analysis of the network.miRNA-149-5p-PDGFRB-lncRNA CTEPH-associated 1 (CTEPHA1) (TCONS_l2_00020587-XLOC_l2_ 010723) and miRNA-338-5p/miRNA-199b-5p-HIF1A-lncRNA CTEPHA1 are related to the development of CTEPH.(Int Heart J 2019; 60: 924-937)

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Identification and Functional Characterization of Hypoxia-Induced Endoplasmic Reticulum Stress Regulating lncRNA (HypERlnc) in Pericytes

Cited by 66 publications

References 28 publications

Noncoding RNAs as therapeutic targets in early stage diabetic kidney disease

Noncoding RNAs as therapeutic targets in early stage diabetic kidney disease

A Missing LNC in Vascular Diseases

miRNA-PDGFRB/HIF1A-lncRNA CTEPHA1 Network Plays Important Roles in the Mechanism of Chronic Thromboembolic Pulmonary Hypertension

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