Our results using a novel double loss-of-function mouse model and primary adult HCFs suggest that SPRR1A knockdown attenuates adverse post-MI remodeling mediated by miR-150 deletion and that miR-150 plays a vital protective role in part by blunting CF activation through its direct functional repression of profibrotic SPRR1A. Here, CFTR is linked to myocardial infarction.