Murray IR, et al. 𝛂v integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis. Nat Commun. 2017 Oct 24;8(1):1118.
Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRb) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRb+ cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on av integrins. Mice in which av integrin is depleted in PDGFRb+ cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of av integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. av integrin blockade also reduces TGFb activation in primary human skeletal muscle and cardiac PDGFRb+ cells, suggesting that av integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.