Abstract

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

Xiaojing Dai 戴晓婧

Sr. Research Scientist

Xiaojing Dai is a Research Scientist at the University of Texas MD Anderson Cancer Center, under the pioneer department of Advanced Genomic Technology Core. She led the SOP, developing laboratory information management systems for advanced genomics sequencing and cell-based assays. She also worked as a research scientist at the University of Texas Health Science Center before her latest role. Before joining UT at MD Anderson, she earned her Ph.D. in the Neuroscience Program at The University of Tokyo and an M.D. from Ningxia Medical University in China. She is also jointly pursuing the Online Master of Science in Computer Science (OMSCS) at Georgia Institute of Technology (GaTech). Her research interests lie in AI for digital pathology, code structure learning, single-cell sequencing in software engineering in health, and medical imaging.