Genome-Wide Identification of Long Noncoding RNAs in Rat Models of Cardiovascular and Renal Disease

Gopalakrishnan, Kathirvel; Kumarasamy, Sivarajan; Mell, Blair; Joe, Bina

doi:10.1161/hypertensionaha.114.04498

Cited by 51 publications

(31 citation statements)

References 51 publications

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“…The quality of all RNA samples was determined using a bio-analyzer (Agilent Technologies, Inc.) before the preparation of the sequencing library. An amount of~1-2 µg of total RNA of each sample was used for RNA-seq library preparation [91]. Briefly, mRNA was enriched from total RNA with NEBNext Poly(A) mRNA Magnetic Isolation Module (NEB, #E7490S), and rRNA was removed with a RiboZero Magnetic Gold Kit (Epicenter, MRZG126).…”

Section: Library Preparation and Sequencingmentioning

confidence: 99%

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

Gopalakrishnan

Kumar

2020

IJMS

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During pregnancy, the uterine artery (UA) undergoes extensive remodeling to permit a 20-40 fold increase in blood flow with associated changes in the expression of a multitude of genes. This study used next-gen RNA sequencing technology to identify pathways and genes potentially involved in arterial adaptations in pregnant rat UA (gestation day 20) compared with non-pregnant rat UA (diestrus). A total of 2245 genes were differentially expressed, with 1257 up-regulated and 970 down-regulated in pregnant UA. Gene clustering analysis revealed a unique cluster of suppressed genes implicated in calcium signaling pathway and vascular smooth muscle contraction in pregnant UA. Transcription factor binding site motif scanning identified C2H2 ZF, AP-2 and CxxC as likely factors functional on the promoters of down-regulated genes involved in calcium signaling and vascular smooth muscle contraction. In addition, 1686 genes exhibited alternative splicing that were mainly implicated in microtubule organization and smooth muscle contraction. Cross-comparison analysis identified novel genes that were both differentially expressed and alternatively spliced; these were involved in leukocyte and B cell biology and lipid metabolism. In conclusion, this first comprehensive study provides a valuable resource for understanding the molecular mechanism underlying gestational uterine arterial adaptations during pregnancy. RAMP])[15], calcium and potassium channels [16,17], growth factor genes (vascular endothelial growth factor [VEGF], placental growth factor, insulin-like growth factor 1 [IGF-I] and bone morphogenetic protein 6 [BMP6], vasodilator genes (nitric oxide (endothelial nitric oxide synthase), and hydrogen sulfide [cystathionine β-synthase]) [3,18] in uterine vasculature during pregnancy significantly impact vascular remodeling and vasodilation. Furthermore, several other signaling pathways have been implicated in arterial remodeling, including matrix metalloproteinases (MMP) activation [19], adrenergic influences [20], toll-like receptors [21], cytoskeleton [22], including vimentin [23], and membrane-associated tyrosine kinases such as PYK2 [24]. These studies were conducted in isolation, and surprisingly, no studies have comprehensively examined global transcriptome and the associated pathways involved in normal gestational uterine vascular adaptations.Another missing link is whether post-transcriptional regulation also contributes to the functions of key genes that modulate pregnancy mediated uterine vascular adaptations. Although the pre-mRNAs are transcribed from a single gene locus, through the alternative splicing, like differential exon inclusion or skipping, the pre-mRNAs can be spliced into different ways to generate divergent isoforms [25,26]. These new isoforms often result in interaction profiles that are divergent from the 'canonical' isoform [27]. There is only one study that discovered changes in alternative splicing of guanylyl cyclase, a major vasodilatory mediator, in the pregnant ovine UA [28]. Thus, whether...

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Section: Library Preparation and Sequencingmentioning

confidence: 99%

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

Gopalakrishnan

Kumar

2020

IJMS

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“…Despite these ‘ inconvenient truths ’, the Dahl rat has been a powerful genetic model that has paved the way of our understanding of the contributions of genetics to the pathophysiological processes underlying the onset and progression of hypertension 48, 68, 85, 87, 100, 107–109 . Most of the research on the genetics of hypertension using the Dahl rat as an experimental model has focused on the autosomes.…”

Section: Perspectivesmentioning

confidence: 99%

Dr Lewis Kitchener Dahl, the Dahl Rats, and the “Inconvenient Truth” About the Genetics of Hypertension

Joe

2015

Hypertension

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Synopsis Lewis K. Dahl is regarded as an iconic figure in the field of hypertension research. During the 1960s and 1970s he published several seminal articles in the field that shed light on the relationship between salt and hypertension. Further, the Dahl rat models of hypertension that he developed by a selective breeding strategy are among the most widely used models for hypertension research. To this day, genetic studies using this model are ongoing in our laboratory. While Dr. Dahl is known for his contributions to the field of hypertension, very little, if any, of his personal history is documented. This article details a short biography of Dr. Lewis Dahl, the history behind the development of the Dahl rats and presents an overview of the results obtained through the genetic analysis of the Dahl rat as an experimental model to study the inheritance of hypertension.

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“…showed differentially expressed lncRNAs between Dahl salt-sensitive (S) versus Dahl salt-resistant (R) and Dahl salt-sensitive versus spontaneously hypertensive rat (SHR) comparisons, respectively [122]. They identified 3273 transcripts as rat lncRNAs, and detected differential expression of 273 lncRNAs between S versus R rats.…”

Section: Introductionmentioning

confidence: 99%

“…Pex11b is also reported to correlate with fat metabolism, insulin, and blood sugar-related traits in SHR [128]. Decrease of Pex11b and increase of Sp5 protein may be related to metabolic futures of S rat [122]. Nagase et al .…”

Section: Introductionmentioning

confidence: 99%

Non-coding RNAs and Hypertension–Unveiling Unexpected Mechanisms of Hypertension by the Dark Matter of the Genome

Murakami¹

2015

CHYR

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Hypertension is a major risk factor of cardiovascular diseases and a most important health problem in developed countries. Investigations on pathophysiology of hypertension have been based on gene products from coding region that occupies only about 1% of total genome region. On the other hand, non-coding region that occupies almost 99% of human genome has been regarded as “junk” for a long time and went unnoticed until these days. But recently, it turned out that non-coding region is extensively transcribed to non-coding RNAs and has various functions. This review highlights recent updates on the significance of non-coding RNAs such as micro RNAs and long non-coding RNAs (lncRNAs) on the pathogenesis of hypertension, also providing an introduction to basic biology of non-coding RNAs. For example, microRNAs are associated with hypertension via neuro-fumoral factor, sympathetic nerve activity, ion transporters in kidneys, endothelial function, vascular smooth muscle phenotype transformation, or communication between cells. Although reports of lncRNAs on pathogenesis of hypertension are scarce at the moment, new lncRNAs in relation to hypertension are being discovered at a rapid pace owing to novel techniques such as microarray or next-generation sequencing. In the clinical settings, clinical use of non-coding RNAs in identifying cardiovascular risks or developing novel tools for treating hypertension such as molecular decoy or mimicks is promising, although improvement in chemical modification or drug delivery system is necessary.

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Genome-Wide Identification of Long Noncoding RNAs in Rat Models of Cardiovascular and Renal Disease

Cited by 51 publications

References 51 publications

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

Dr Lewis Kitchener Dahl, the Dahl Rats, and the “Inconvenient Truth” About the Genetics of Hypertension

Non-coding RNAs and Hypertension–Unveiling Unexpected Mechanisms of Hypertension by the Dark Matter of the Genome

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