alpha v integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis

作者：Murray I R; Gonzalez Z N; Baily J; Dobie R; Wallace R J; Mackinnon A C; Smith J R; Greenhalgh S N; Thompson A I; Conroy K P; Griggs D W; Ruminski P G; Gray G A; Singh M; Campbell M A; Kendall T J; Dai J; Li Y; Iredale J P; Simpson H; Huard J; Peault B^*; Henderson N C^*

来源：Nature Communications, 2017, 8(1): 1118.

DOI：10.1038/s41467-017-01097-z

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.

• 出版日期2017-10-24
• 单位UT Health