资源环境科技发展态势分析平台

Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFR beta) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFR beta(+) cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on alpha v integrins. Mice in which av integrin is depleted in PDGFR beta(+) 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. alpha v integrin blockade also reduces TGF beta activation in primary human skeletal muscle and cardiac PDGFR beta(+) cells, suggesting that av integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.