MiR-21 and cardiac fibrosis. Another brick in the wall?

Organ fibrosis is a common final pathway of long-lasting and iterative tissue fibrosis, and is present in several pathologies, including ischaemic heart disease, diabetes mellitus, hypertension, and chronic kidney disease. Thus, it represents a widespread cause of morbidity and mortality. Tissue fibrosis is characterized by an excessive and uncontrolled deposition of extracellular matrix (ECM) elements. The development of fibrosis requires: (i) increased synthesis by matrix metalloproteinases (MMPs) and decreased degradation of ECM due to down-regulation of MMP inhibitors; (ii) the stimulation of profibrotic mediators, such as transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and cytokines; (iii) the differentiation of fibroblasts into myofibroblasts, which express features of smooth muscle differentiation; and (iv) the recruitment of cells of an endothelial origin for endothelial to mesenchymal transition (EndMT), generating cells that still express endothelial markers while gaining fibroblast-like characteristics. In addition, innate and adaptive immune responses play an important role in development of fibrosis. Despite recent advances in the understanding of the mechanisms underlying its development, therapeutic strategies specifically aimed at fibrosis remain limited.