RGD Reference Report - MicroRNA-214-3p in the Kidney Contributes to the Development of Hypertension. - Rat Genome Database

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MicroRNA-214-3p in the Kidney Contributes to the Development of Hypertension.

Authors: Liu, Yong  Usa, Kristie  Wang, Feng  Liu, Pengyuan  Geurts, Aron M  Li, Junhui  Williams, Anna Marie  Regner, Kevin R  Kong, Yiwei  Liu, Han  Nie, Jing  Liang, Mingyu 
Citation: Liu Y, etal., J Am Soc Nephrol. 2018 Oct;29(10):2518-2528. doi: 10.1681/ASN.2018020117. Epub 2018 Jul 26.
RGD ID: 38500245
Pubmed: PMID:30049682   (View Abstract at PubMed)
PMCID: PMC6171279   (View Article at PubMed Central)
DOI: DOI:10.1681/ASN.2018020117   (Journal Full-text)


BACKGROUND: In spite of extensive study, the mechanisms for salt sensitivity of BP in humans and rodent models remain poorly understood. Several microRNAs (miRNAs) have been associated with hypertension, but few have been shown to contribute to its development.
METHODS: We examined miRNA expression profiles in human kidney biopsy samples and rat models using small RNA deep sequencing. To inhibit an miRNA specifically in the kidney in conscious, freely moving rats, we placed indwelling catheters to allow both renal interstitial administration of a specific anti-miR and measurement of BP. A rat with heterozygous disruption of the gene encoding endothelial nitric oxide synthase (eNOS) was developed. We used bioinformatic analysis to evaluate the relationship between 283 BP-associated human single-nucleotide polymorphisms (SNPs) and 1870 human miRNA precursors, as well as other molecular and cellular methods.
RESULTS: Compared with salt-insensitive SS.13BN26 rats, Dahl salt-sensitive (SS) rats showed an upregulation of miR-214-3p, encoded by a gene in the SS.13BN26 congenic region. Kidney-specific inhibition of miR-214-3p significantly attenuated salt-induced hypertension and albuminuria in SS rats. miR-214-3p directly targeted eNOS. The effect of miR-214-3p inhibition on hypertension and albuminuria was abrogated in SS rats with heterozygous loss of eNOS. Human kidney biopsy specimens from patients with hypertension or hypertensive nephrosclerosis showed upregulation of miR-214-3p; the gene encoding miR-214-3p was one of several differentially expressed miRNA genes located in proximity to human BP-associated SNPs.
CONCLUSIONS: Renal miR-214-3p plays a functional and potentially genetic role in the development of hypertension, which might be mediated in part by targeting eNOS.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MIR214Humanhypertension  IEP RNA:increased expression:kidneyRGD 
Mir214Mousehypertension  ISOMIR214 (Homo sapiens)RNA:increased expression:kidneyRGD 
Mir214Rathypertension treatmentIMP  RGD 
Mir214Rathypertension  ISOMIR214 (Homo sapiens)RNA:increased expression:kidneyRGD 
MIR214HumanHypertensive Nephrosclerosis  IEP RNA:increased expression:kidneyRGD 
Mir214MouseHypertensive Nephrosclerosis  ISOMIR214 (Homo sapiens)RNA:increased expression:kidneyRGD 
Mir214RatHypertensive Nephrosclerosis  ISOMIR214 (Homo sapiens)RNA:increased expression:kidneyRGD 
MIR214Humanrenal hypertension amelioratesISOMir214 (Rattus norvegicus) RGD 
Mir214Mouserenal hypertension amelioratesISOMir214 (Rattus norvegicus) RGD 
Mir214Ratrenal hypertension amelioratesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir214  (microRNA 214)

Genes (Mus musculus)
Mir214  (microRNA 214)

Genes (Homo sapiens)
MIR214  (microRNA 214)

Objects referenced in this article
Strain SS-Nos3em13Mcwi null Rattus norvegicus

Additional Information