MiR‐322‐5p targets IGF‐1 and is suppressed in the heart of rats with pulmonary hypertension. Issue 3 (24th January 2018)

• Record Type: Journal Article
• Authors: Connolly, Martin; Garfield, Benjamin E.; Crosby, Alexi; Morrell, Nick W.; Wort, Stephen J.; Kemp, Paul R.
• Is Part Of: FEBS open bio. Volume 8:Issue 3(2018)
• Page Start: 339
• Page End: 348
• Publication Date: 2018-01-24
• Subjects: IGF‐1 -- miR‐322/424 -- pulmonary arterial hypertension -- right ventricular hypertrophy; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12369
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : 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. Abstract : 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.