Credit: Thomas Deerinck, NCMIR / Science Source

MicroRNAs (miRNAs) packaged in microvesicles or exosomes can help cells communicate with one another. Claudia Bang and her colleagues now show that this type of cell-cell interaction occurs between cardiac fibroblasts and muscle cells in culture and may promote pathological heart growth in mice (J. Clin. Invest. 124, 2136–2146, 2014).

After showing that cultured cardiac fibroblasts release miRNA-containing exosomes, the authors found that one of these miRNAs, miR-21*, was transferred specifically into cultured cardiac muscle cells, causing an increase in their size. The authors then identified the gene encoding SORBS2 as a direct miR-21* target in the muscle cells. SORBS2 and another protein, PDLIM5, are good candidates for mediating the effect of miR-21* on cardiac muscle cell size, as deficiency of either protein led to increased cell size. In mice with pathological heart growth, the amounts of miR-21* in pericardial heart fluid were increased, and intravenous administration of a miR-21* antagomir reduced heart growth.

Although the 'passenger' or 'star' strand of miRNAs precursors is often degraded, the finding that cardiac fibroblast–derived exosomes were enriched in star strands—including miR-21*—points to the possibility that star strands might be preferentially involved in exosome-mediated communication.