?v integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.

ABSTRACT: Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFR?) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFR?⁺ cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on ?v integrins. Mice in which ?v integrin is depleted in PDGFR?⁺ cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of ?v integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. ?v integrin blockade also reduces TGF? activation in primary human skeletal muscle and cardiac PDGFR?⁺ cells, suggesting that ?v integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.

SUBMITTER: Murray IR 

PROVIDER: S-EPMC5653645 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature