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αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis

Author

Listed:
  • I. R. Murray

    (University of Edinburgh
    University of Edinburgh)

  • Z. N. Gonzalez

    (University of Edinburgh)

  • J. Baily

    (University of Edinburgh)

  • R. Dobie

    (University of Edinburgh)

  • R. J. Wallace

    (University of Edinburgh)

  • A. C. Mackinnon

    (University of Edinburgh)

  • J. R. Smith

    (University of Edinburgh)

  • S. N. Greenhalgh

    (University of Edinburgh)

  • A. I. Thompson

    (University of Edinburgh)

  • K. P. Conroy

    (University of Edinburgh)

  • D. W. Griggs

    (Edward A. Doisy Research Center)

  • P. G. Ruminski

    (Edward A. Doisy Research Center)

  • G. A. Gray

    (University of Edinburgh)

  • M. Singh

    (Edward A. Doisy Research Center)

  • M. A. Campbell

    (Edward A. Doisy Research Center)

  • T. J. Kendall

    (University of Edinburgh)

  • J. Dai

    (University of Texas McGovern Medical School
    The University of Texas Health Science Center at Houston (UT Health))

  • Y. Li

    (University of Texas McGovern Medical School
    The University of Texas Health Science Center at Houston (UT Health))

  • J. P. Iredale

    (University of Bristol)

  • H. Simpson

    (University of Edinburgh)

  • J. Huard

    (Steadman Philippon Research Institute
    Medical School at Houston)

  • B. Péault

    (University of Edinburgh
    University of California)

  • N. C. Henderson

    (University of Edinburgh)

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.

Suggested Citation

  • I. R. Murray & Z. N. Gonzalez & J. Baily & R. Dobie & R. J. Wallace & A. C. Mackinnon & J. R. Smith & S. N. Greenhalgh & A. I. Thompson & K. P. Conroy & D. W. Griggs & P. G. Ruminski & G. A. Gray & M., 2017. "αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01097-z
    DOI: 10.1038/s41467-017-01097-z
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