Periostin is a Pivotal Target of microRNA-150-5p in Cardiac Fibroblast Activation and Chronic Myocardial Infarction

Abstract

Our prior studies have revealed that miR-150-5p (miR-150) attenuated cardiac dysfunction in mice, which overexpressed a long noncoding RNA called myocardial infarction–associated transcript during myocardial infarction or harbored cardiac-specific abrogation of β-arrestin–mediated β₁-adrenergic receptor signaling during chronic catecholamine stimulation. Although previous studies have shown the importance of miR-150 in heart failure, details surrounding its actions remain elusive in part because of (1) the lack of detailed mechanistic insight by which this small noncoding RNA induces myocardial protection and (2) the absence of definitive studies using appropriate mouse models to establish its direct functional relationship with key downstream targets. In the current study, we provide strong evidence that fibrotic periostin is a significant downstream target of miR-150 repression in ischemic mouse hearts. To the best of our knowledge, this is the first study to directly establish the functional link between miR-150 and periostin in murine myocardial infarction and primary adult human cardiac fibroblast activation.