MiR-1-5p targets TGF-ßR1 and is suppressed in the hypertrophying hearts of rats with pulmonary arterial hypertension

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs, implicated in the control of myocardial homeostasis. miR-1 has been shown to be down-regulated in hypertrophying rodent hearts and its restoration an ameliorating factor. We used monocrotaline treatment to induce pulmonary hypertension in a cohort of rats and thereafter-showed miR-1 expression was reduced in the hypertrophying right ventricle (RV) (Fig. 1A). Bioinformatic analysis identified TGF-βR1 (ALK5) as a predicted target for miR-1, the expression of which was increased in the RV (Fig. 1B, C). Cell transfection with a miR-1-mimic reduced GFP expression from a reporter vector containing the ALK5 3’-UTR and also knocked down endogenous ALK5. Lastly, miR-1 reduced TGF-β activation of a SMAD2/3-dependent reporter. Taken together, these data confirm miR-1 targets TGF-βR1 thereby reducing TGF-β signalling, which may regulate cardiac hypertrophy.