miR‐322‐5p targets IGF‐1 and is suppressed in the heart of rats with pulmonary hypertension

Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular hypertrophy. Here, we show that miR‐322‐5p (the rodent orthologue of miR‐424‐5p) expression is decreased in the right ventricle of monocrotaline‐treated rats, a model of PA...

Full description

Saved in:
Bibliographic Details
Published in:FEBS open bio 2018-03, Vol.8 (3), p.339-348
Main Authors: Connolly, Martin, Garfield, Benjamin E., Crosby, Alexi, Morrell, Nick W., Wort, Stephen J., Kemp, Paul R.
Format: Article
Language:English
Subjects:
3' Untranslated regions
Animals
Argonaute 2 protein
Cell division
Experiments
Growth factors
Heart
Hypertension
Hypertrophy
IGF‐1
Insulin
Insulin-like growth factors
Kinases
Medical prognosis
MicroRNAs
miR‐322/424
Monocrotaline
mRNA
Musculoskeletal system
Protein expression
Protein folding
Protein synthesis
Proteins
pulmonary arterial hypertension
Pulmonary hypertension
right ventricular hypertrophy
Transfection
Ventricle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular hypertrophy. Here, we show that miR‐322‐5p (the rodent orthologue of miR‐424‐5p) expression is decreased in the right ventricle of monocrotaline‐treated rats, a model of PAH, whereas a putative target insulin‐like growth factor 1 (IGF‐1) is increased. IGF‐1 mRNA was enriched 16‐fold in RNA immunoprecipitated with Ago2, indicating binding to miR‐322‐5p. In cell transfection experiments, miR‐322‐5p suppressed the activity of a luciferase reporter containing a section of the IGF‐1 3′ untranslated region (UTR) as well as IGF‐1 mRNA and protein levels. Taken together, these data suggest that miR‐322 targets IGF‐1, a process downregulated in PAH‐related RV hypertrophy. miRNA regulate various cell processes, which often go awry in disease. Here, we look at miR‐322‐5p, a miRNA downregulated in the hypertrophying right ventricle of rats with drug‐induced pulmonary arterial hypertension (PAH). Concomitantly, IGF‐1 is upregulated in these enlarged right ventricles. We confirmed that miR‐322‐5p targets IGF‐1, raising the possibility that reduced miR‐322‐5p contributes to the development of hypertrophy in PAH. By Mariana Ruiz [Public domain], via Wikimedia Commons.
ISSN:2211-5463
2211-5463
DOI:10.1002/2211-5463.12369